Imaging the pharmacokinetics and pharmacodynamics of intrathecally administered antisense oligonucleotides in the rat

1Neurosci. Drug Discovery, Ionis Pharmaceuticals, Inc., Carlsbad, CA; 2inviCRO, LLC, Boston, MA; 3Biogen, Inc., Cambridge, MA; 4United Neurosci., Dublin, Ireland

Amyloid load is a more sensitive biomarker for Alzheimer’s imaging

Matt O’Connor

Optimizing the radiosynthesis of 68GaDOTA-MLN6907 peptide containing three disulfide cyclization bonds – a GCC specific chelate for clinical radiopharmaceuticals

Author links open overlay panelAnchalGhaiaBaljinderSinghaMengshiLibfTamara A.DanielscRichardCoelhodKellyOrcuttd1G. LeonardWatkinsbJeffrey P.NorenbergcDonnaCvete2Michael K.Schultzbf13

New horizons within sight for haemophilia

Author links open overlay panelH. Marijke van den Berg

Dual-isotope Cryo-imaging Quantitative Autoradiography (CIQA): Anvestigating Antibody-Drug Conjugate Distribution And Payload Delivery Through Imaging

Author links open overlay panelIlovich O1, Qutaish M2, Hesterman JY2, Orcutt K2, Hoppin J2, Polyak I2, Seaman M2, Abu-Yousif AO3, Cvet D3, Bradley DP3.

The Perivascular Pathways for Influx of Cerebrospinal Fluid are Most Efficient in the Midbrain

Dobson H1,2,3, Sharp MM4, Cumpsty R4, Criswell TP4, Wellman T1, Finucane C1, Sullivan JM1, Weller RO4, Verma A5, Carare RO6.



A First Time in Human, Microdose, Positron Emission Tomography Study of the Safety, Immunogenicity, Biodistribution and Radiation Dosimetry of 18F FB-A20FMDV2 for Imaging the Integrin αvβ6.

Keat N, Kenny J, Chen K, Onega M, Garman N, Slack RJ, Parker CA, Lumbers T, Hallett W, Saleem A, Passchier J, Lukey PT.
J Nucl Med Technol. 2018 Feb 2;. [Epub ahead of print]
PMID: 29438002 [PubMed – as supplied by publisher]

Semi-Automated Analysis of Diaphragmatic Motion with Dynamic Magnetic Resonance Imaging in Healthy Controls and Non-Ambulant Subjects with Duchenne Muscular Dystrophy.

Bishop CA, Ricotti V, Sinclair CDJ, Evans MRB, Butler JW, Morrow JM, Hanna MG, Matthews PM, Yousry TA, Muntoni F, Thornton JS, Newbould RD, Janiczek RL.
Front Neurol. 2018;9:9.
PMID: 29434565 [PubMed]

Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

Roseman L, Demetriou L, Wall MB, Nutt DJ, Carhart-Harris RL.
Neuropharmacology. 2017 Dec 27. pii: S0028-3908(17)30639-1. doi: 10.1016/j.neuropharm.2017.12.041. [Epub ahead of print] Review.
PMID: 29288686

Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration.

Scott G, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, Feeney C, Owen DR, Lingford-Hughes A, Howes O, Patel MC, Goldstone AP, Gunn RN, Blennow K, Matthews PM, Sharp DJ.
Brain. 2017 Dec 19;. [Epub ahead of print]
PMID: 29272357 [PubMed – as supplied by publisher]

Use of carbon-11 labelled tool compounds in support of drug development.

Boscutti G, Huiban M, Passchier J.
Drug Discov Today Technol. 2017 Nov;25:3-10. doi: 10.1016/j.ddtec.2017.11.009. Epub 2017 Dec 1. Review.
PMID: 29233265

Imaging synaptic density: A different look at neurological diseases.

Rabiner EIA.
J Nucl Med. 2017 Nov 9. pii: jnumed.117.198317. doi: 10.2967/jnumed.117.198317. [Epub ahead of print] No abstract available.
PMID: 29123011

TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis.

Owen DR, Fan J, Campioli E, Venugopal S, Midzak A, Daly E, Harlay A, Issop L, Libri V, Kalogiannopoulou D, Oliver E, Gallego-Colon E, Colasanti A, Huson L, Rabiner EA, Suppiah P, Essagian C, Matthews PM, Papadopoulos V.
Biochem J. 2017 Nov 21;474(23):3985-3999. doi: 10.1042/BCJ20170648.
PMID: 29074640 Free PMC Article

Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic and clinical evolution at follow up.

Mauri MC, Di Pace C, Reggiori A, Paletta S, Colasanti A.
Asian J Psychiatr. 2017 Oct;29:117-122. doi: 10.1016/j.ajp.2017.04.014. Epub 2017 May 2.
PMID: 29061407

Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis.

Datta G, Colasanti A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Van Vlierberghe E, Van Hecke W, Searle G, Santos-Ribeiro A, Matthews PM.
Brain. 2017 Nov 1;140(11):2927-2938. doi: 10.1093/brain/awx228.
PMID: 29053775

Comparison of four 11C-labeled PET ligands to quantify translocator protein 18 kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176-based on recent publications that measured specific-to-non-displaceable ratios.

Fujita M, Kobayashi M, Ikawa M, Gunn RN, Rabiner EA, Owen DR, Zoghbi SS, Haskali MB, Telu S, Pike VW, Innis RB.
EJNMMI Res. 2017 Oct 16;7(1):84. doi: 10.1186/s13550-017-0334-8.
PMID: 29038960 Free PMC Article

Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms.

Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Pannekoek JN, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJ.
Sci Rep. 2017 Oct 13;7(1):13187. doi: 10.1038/s41598-017-13282-7.
PMID: 29030624 Free PMC Article

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion.

Freeman TP, Pope RA, Wall MB, Bisby JA, Luijten M, Hindocha C, Mokrysz C, Lawn W, Moss A, Bloomfield MAP, Morgan CJA, Nutt DJ, Curran HV.
Int J Neuropsychopharmacol. 2017 Sep 2. doi: 10.1093/ijnp/pyx082. [Epub ahead of print]
PMID: 29025134

The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory ‘M1’ human macrophages.

Narayan N, Mandhair H, Smyth E, Dakin SG, Kiriakidis S, Wells L, Owen D, Sabokbar A, Taylor P.
PLoS One. 2017 Oct 2;12(10):e0185767. doi: 10.1371/journal.pone.0185767. eCollection 2017.
PMID: 28968465 Free PMC Article

Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

Bonsall DR, Kokkinou M, Veronese M, Coello C, Wells LA, Howes OD.
J Neurochem. 2017 Dec;143(5):551-560. doi: 10.1111/jnc.14223. Epub 2017 Oct 26.
PMID: 28921596

Thermal imaging is a non-invasive alternative to PET-CT for measurement of brown adipose tissue activity in humans.

Law JM, Morris DE, Izzi-Engbeaya C, Salem V, Coello C, Robinson L, Jayasinghe M, Scott R, Gunn R, Rabiner E, Tan T, Dhillo W, Bloom S, Budge H, Symonds M.
J Nucl Med. 2017 Sep 14. pii: jnumed.117.190546. doi: 10.2967/jnumed.117.190546. [Epub ahead of print]
PMID: 28912148

Respiratory magnetic resonance imaging biomarkers in Duchenne muscular dystrophy.

Mankodi A, Kovacs W, Norato G, Hsieh N, Bandettini WP, Bishop CA, Shimellis H, Newbould RD, Kim E, Fischbeck KH, Arai AE, Yao J.
Ann Clin Transl Neurol. 2017 Jul 28;4(9):655-662. doi: 10.1002/acn3.440. eCollection 2017 Sep.
PMID: 28904987 Free PMC Article

Investigating the neural correlates of smoking: Feasibility and results of combining electronic cigarettes with fMRI.

Wall MB, Mentink A, Lyons G, Kowalczyk OS, Demetriou L, Newbould RD.
Sci Rep. 2017 Sep 12;7(1):11352. doi: 10.1038/s41598-017-11872-z.
PMID: 28900267 Free PMC Article

Erratum to: Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer.intoErratum to: Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer.

Saleem A, Searle GE, Kenny LM, Huiban M, Kozlowski K, Waldman AD, Woodley L, Palmieri C, Lowdell C, Kaneko T, Murphy PS, Lau MR, Aboagye EO, Coombes RC.
EJNMMI Res. 2017 Sep 8;7(1):74. doi: 10.1186/s13550-017-0323-y. No abstract available.
PMID: 28887806 Free PMC Article

PET Tau and Amyloid-β Burden in Mild Alzheimer’s Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.

Koychev I, Gunn RN, Firouzian A, Lawson J, Zamboni G, Ridha B, Sahakian BJ, Rowe JB, Thomas A, Rochester L, Ffytche D, Howard R, Zetterberg H, MacKay C, Lovestone S; Deep and Frequent Phenotyping study team (.
J Alzheimers Dis. 2017;60(1):283-293. doi: 10.3233/JAD-170129.
PMID: 28800330 Free PMC Article

Relationships between the integrity and function of lumbar nerve roots as assessed by diffusion tensor imaging and neurophysiology.

Chiou SY, Hellyer PJ, Sharp DJ, Newbould RD, Patel MC, Strutton PH.
Neuroradiology. 2017 Sep;59(9):893-903. doi: 10.1007/s00234-017-1869-0. Epub 2017 Jul 25.
PMID: 28744730 Free PMC Article

Quantification of human brain PDE4 occupancy by GSK356278: A [11C](R)-rolipram PET study.

van der Aart J, Salinas C, Dimber R, Pampols-Maso S, Weekes AA, Tonkyn J, Gray FA, Passchier J, Gunn RN, Rabiner EA.
J Cereb Blood Flow Metab. 2017 Jan 1:271678X17720868. doi: 10.1177/0271678X17720868. [Epub ahead of print]
PMID: 28737056

Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits.

Niccolini F, Wilson H, Pagano G, Coello C, Mehta MA, Searle GE, Gunn RN, Rabiner EA, Foltynie T, Politis M.
Neurology. 2017 Jul 12. pii: 10.1212/WNL.0000000000004201. doi: 10.1212/WNL.0000000000004201. [Epub ahead of print]

Quantitative analysis of dynamic 18F-FDG PET/CT for measurement of lung inflammation.

Coello C, Fisk M, Mohan D, Wilson FJ, Brown AP, Polkey MI, Wilkinson I, Tal-Singer R, Murphy PS, Cheriyan J, Gunn RN.
EJNMMI Res. 2017 Dec;7(1):47. doi: 10.1186/s13550-017-0291-2. Epub 2017 May 25.

Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans.

Owen DR, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhair H, Peferoen LA, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CS.
J Cereb Blood Flow Metab. 2017 Jan 1:271678X17710182. doi: 10.1177/0271678X17710182. [Epub ahead of print]

Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson’s disease.

Martin-Bastida A, Ward RJ, Newbould R, Piccini P, Sharp D, Kabba C, Patel MC, Spino M, Connelly J, Tricta F, Crichton RR, Dexter DT.
Sci Rep. 2017 May 3;7(1):1398. doi: 10.1038/s41598-017-01402-2.

11 C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11 C-( R )-PK11195

Kobayashi M, Jiang T, Telu S, Zoghbi SS, Gunn RN, Rabiner EA, Owen DR, Guo Q, Pike VW, Innis RB, Fujita M.
J Cereb Blood Flow Metab. 2017 Jan 1:271678X17699223. doi: 10.1177/0271678X17699223. [Epub ahead of print]

[11C]PBR28 or [18F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis.

Datta G, Colasanti A, Kalk N, Owen DR, Scott G, Rabiner EI, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nie L, Battaglini M, De Stefano N, Matthews P.
J Nucl Med. 2017 Mar 16. pii: jnumed.116.187161. doi: 10.2967/jnumed.116.187161. [Epub ahead of print]

Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals.

Morris LS, Baek K, Tait R, Elliott R, Ersche KD, Flechais R, McGonigle J, Murphy A, Nestor LJ, Orban C, Passetti F, Paterson LM, Rabiner I, Reed L, Smith D, Suckling J, Taylor EM, Bullmore ET, Lingford-Hughes AR, Deakin B, Nutt DJ, Sahakian BJ, Robbins TW, Voon V; ICCAM Consortium.
Addict Biol. 2017 Feb 28. doi: 10.1111/adb.12503. [Epub ahead of print]

Nalmefene Reduces Reward Anticipation in Alcohol Dependence: An Experimental Functional Magnetic Resonance Imaging Study.

Quelch DR, Mick I, McGonigle J, Ramos AC, Flechais RS, Bolstridge M, Rabiner E, Wall MB, Newbould RD, Steiniger-Brach B, van den Berg F, Boyce M, Østergaard Nilausen D, Breuning Sluth L, Meulien D, von der Goltz C, Nutt D, Lingford-Hughes A.
Biol Psychiatry. 2017 Jan 10. pii: S0006-3223(17)30008-2. doi: 10.1016/j.biopsych.2016.12.029. [Epub ahead of print]

Neural substrates of cue reactivity and craving in gambling disorder

E H Limbrick-Oldfield, I Mick, R E Cocks, J McGonigle, S P Sharman, A P Goldstone, P R A Stokes, A Waldman, D Erritzoe, H Bowden-Jones, D Nutt, A Lingford-Hughes and L Clark
Citation: Translational Psychiatry (2017) 7, e992; doi:10.1038/tp.2016.256
Published online 3 January 2017

Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study

Kalk NJ, Guo Q, Owen D, Cherian R, Erritzoe D, Gilmour A, Ribeiro AS, McGonigle J, Waldman A, Matthews P, Cavanagh J, McInnes I, Dar K, Gunn R, Rabiner EA, Lingford-Hughes AR.
Transl Psychiatry. 2017 Jan 10;7(1):e996. doi: 10.1038/tp.2016.264.

Imaging in Central Nervous System Drug Discovery

Gunn RN, Rabiner EA.
Semin Nucl Med. 2017 Jan;47(1):89-98. doi: 10.1053/j.semnuclmed.2016.09.001. Review.
PMID: 27987561

T2 relaxation mapping MRI of healthy and inflamed gingival tissue

Newbould RD, Bishop CA, Janiczek RL, Parkinson C, Hughes FJ.
Dentomaxillofac Radiol. 2017 Feb;46(2):20160295. doi: 10.1259/dmfr.20160295.
PMID: 27936919

Quantification of Lung PET Images: Challenges and Opportunities

Delphine L Chen, Joseph Cheriyan, Edwin Chilvers, Gourab Choudoury, Christopher Coello, Martin Connell, Marie Fisk, Ashley M Groves, Roger N Gunn, Beverley F Holman, Brian F Hutton, Sarah Lee, William MacNee, Divya Mohan, David Parr, Deepak Subramanian, Ruth Tal-Singer, Kris Thielemans, Edwin JR van Beek, Laurence Vass, Jeremy W Wellen, Ian Wilkinson and Frederick J Wilson
J Nucl Med January 12, 2017 jnumed.116.184796

The Structure of the Perivascular Compartment in the Old Canine Brain: A Case Study


The Expansion of Heterotopic Bone in Fibrodysplasia Ossificans Progressiva is Activin A-Dependent†

Kinetic modeling, test-retest, and dosimetry of 123I-MNI-420 in humans.

Three-Dimensional Dosimetry for Radiation Safety Estimates from Intrathecal Administration

High-throughput high-volume nuclear imaging for preclinical in vivo compound screening

The phosphodiesterase 10 positron emission tomography tracer, 18FMNI-659, as a novel biomarker for early Huntington disease

Advancing Drug Discovery and Development Using Molecular Imaging (ADDMI): an Interest Group of the World Molecular Imaging Society and an Inaugural Session on Positron Emission Tomography (PET)

In vivo evaluation of 18F-MNI698: an 18F-labeled radiotracer for imaging of serotonin 4 receptors in brain


Automated segmentation of MR imaging to determine normative central nervous system cerebrospinal fluid volumes in healthy volunteers

Whole-body biodistribution and dosimetry estimates of a novel radiotracer for imaging of serotonin 4 receptors in brain: 18FMNI-698


14C-2-deoxyglucose autoradiography screen for mouse brain activity: relating known therapeutics and novel compounds for schizophrenia, depression, and bipolar disorder to brain circuitry


Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-β

The Effect of Bolus Volume and Mechanical Forces on the Biodistribution of ASOs Following Lumbar Intrathecal Administration in Cynomolgus Monkeys (S38.007)

Kinetic Modeling of the Tau PET Tracer 18F-AV-1451 in Human Healthy Volunteers and Alzheimer’s Disease Subjects

Synthesis and in vivo Evaluation of Fluorine-18 and Iodine-123 Pyrazolo 4,3-e -1,2,4-triazolo 1,5-c pyrimidine Derivatives as PET and SPECT Radiotracers for Mapping A2A Receptors

Cerebellar Amyloid-b Plaques: How Frequent Are They, and Do They Influence 18F-Florbetaben SUV Ratios?

Comparison of 11CTZ1964B and 18FMNI659 for PET imaging brain PDE10A in nonhuman primates

Kinetic Modeling of the Tau PET Tracer 18F-AV-1451 in Human Healthy Volunteers and Alzheimer’s Disease Subjects

Molecular Simulation of Receptor Occupancy and Tumor Penetration of an Antibody and Smaller Scaffolds: Application to Molecular Imaging


A dual-isotope 3D Cryo-Imaging Quantitative Autoradiography (CIQA) Method for Simultaneous and Quantitative Assessment of both Antibody and Drug Conjugate Tumor Distribution and Kinetics

3D Cryo-Imaging and Quantitative Autoradiography (CIQA) for the Evaluation of Radiolabeled Drugs Targeting to Tumor Cells

The Use of PET/CT and Autoradiography to Assess the Distribution of a 124-I Labeled Exogenous Protein Following Intranasal Delivery in Cynomolgus Macaques

The Use of Power Analysis in Small Sample Pre-clinical Imaging Studies

Development and Optimization of Standalone Multi-Wavelength Fluorescence Add-on for a Cryoslicer

Development of enzyme mediated imaging and therapy (EMIT) as a novel theragnostic agent for metastatic prostate cancer

A Gradient-Loadable (64)Cu-chelator for Quantifying Tumor Deposition Kinetics of Nanoliposomal Therapeutics by PET

Muscle RING finger-1 promotes a maladaptive phenotype in chronic hypoxia-induced right ventricular remodeling

Optimizing Central Nervous System Drug Development Using Molecular Imaging

CIQuanT – Bridging the Gap between In Vivo and Ex Vivo Imaging by using Quantitative Whole Body Autoradiography (QWBA), 3D Cryo-Imaging (3DC) Techniques, and PET/CT

2015 International Symposium on Biomedical Imaging; Session: Imaging Applications in the Biopharmaceutical Industry.

Multivariate Study Using Short- and Long-lived Radioisotopes, In Vivo PET/CT and Planar Scintigraphy, and Ex Vivo Autoradiography to Assess Biodistribution and Pharmacokinetics of Bone-Targeting Test Material in a Canine Model

PET/CT clinical protocol design for the novel, first in class 68Ga labeled guanylyl cyclase C targeted peptide MLN6907

AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA.

Receptor occupancy and tumor penetration by antibodies, peptides, and antibody fragments: Molecular simulation of imaging assessment

AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA.

Using radionuclear imaging and mechanistic modeling to assess the therapeutic potential of antibody-drug conjugates (ADCs)

AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. SEE MORE…

In vitro and in vivo investigation of the novel, first-in class, Guanylyl Cyclase C (GCC) targeted 68Ga labeled heat stable peptide MLN6907 for tumor imaging

AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA.

First-in class in vivo imaging of guanylyl cyclase c (GCC) in subcutaneous xenografts

AACR/SNMMI State-of-the-Art Molecular Imaging in Cancer Biology and Therapy: Abstracts.

FcRn Rescues Recombinant Factor VIII Fc Fusion Protein from a VWF Independent FVIII Clearance Pathway in Mouse Hepatocytes

Published: April 23, 2015 DOI: 10.1371/journal.pone.0124930c.

Whole-body organ-level and kidney micro-dosimetric evaluations of 64Cu-loaded HER2/ErbB2-targeted liposomal doxorubicin (64Cu-MM-302) in rodents and primates

EJNMMI Research 2015, 5:24

Receptor Tyrosine Kinase EphA5 Is a Functional Molecular Target in Human Lung Cancer

J Biol Chem. 2015 Mar 20; 290(12): 7345–7359.

Cryoflourescence Tomography (CFT) is an Ex Vivo Tool to Study Anatomy, Physiology, and Drug or Tracer Distribution in Brain and Other Organs

Ex vivo imaging methodologies such as immunohistochemistry, fluorescence imaging, and autoradiography have been used to study anatomy, physiology and drug or tracer distribution in either whole bodies or excised organs.  These methodologies can follow and accompany in vivo imaging studies or serve as stand-alone studies themselves.  Because ex vivo processing is relatively expensive and time consuming, often sections and/or images are taken at large intervals (0.1-1 mm) throughout the entire specimen.  Information is lost in these gaps where sections are not collected or imaged.  Further, if a three dimensional model of the specimen is required, interpolation of largely spaced sections is required and the model may suffer.  We sought to address some of these potential drawbacks by capturing high resolution white light and multispectral (700 and 800 nm) fluorescence images off the block after every pass of the micro or macrotome blade using an intraoperative fluorescence imaging system (Curadel, LLC, Worcester, MA), thus vastly improving the amount of information captured throughout the specimen and decreasing total acquisition time.  We have termed the process of fluorescent and high resolution white light data collection and subsequent co-registration and/or three-dimensional reconstruction, cryofluorescence tomography or CFT. Using our CFT methodology, organs or small animal whole bodies are sectioned at 25 microns and all images are captured and acquired in less than 2 hours, improving some shortcomings of various ex vivo techniques, while enabling the creation of high resolution 3D models.

Marc Seaman, Robert Holt, Paige Czarnecki, Jacob Hesterman, Shailendra Patel, Jack Hoppin, John Frangioni, Ajay Verma

Please contact us at info@invicro.com for access to this poster.

Pharmacokinetic and Pharmacodynamic Imaging of Intrathecally Administered Antisense Oligonucleotides

Antisense oligonucleotides (ASOs) are promising drugs for treating CNS disorders due to their specific targeting and extended pharmacological effect. The development of therapeutics for CNS disorders has been impeded by the inability of most drug molecules to cross the blood brain barrier (BBB) and engage their targets. The intrathecal (IT) dosing route offers a solution for bypassing the BBB and delivering drugs directly to the CNS. However, determining the pharmacokinetics (PK) and pharmacodynamics (PD) presents unique challenges imposed by anatomical and functional properties of the IT space and reliance upon ex vivo histological molecular techniques. We developed an imaging approach using radio and fluorophore-labeled ASOs tracking PK and also employed neuroreceptor targeting ASOs to enable tracking of PD using receptor-targeting radiotracers. Two ASOs were evaluated in this study, one that targets the GABRA1 gene and is expected to reduce GABA A receptor alpha1 activity, the other targeting the MALAT1 housekeeping gene as a control treatment.

Ken Zasadny, Jenna M. Sullivan, Daniel A. Wolf, Curt Mazur, Berit Powers, Jacob Hesterman, Marc Seaman, Robert W. Holt, Mohammed Qutaish, Ildiko Polyak, Richard Coelho, Vijay Gottumukkala, Carolynn M. Gaut, Jack Hoppin, Eric E. Swayze, Ajay Verma

Please contact us at info@invicro.com for access to this poster.

SPECT Imaging in a Mouse Model of Muscular Dystrophy: MDX mice have a higher uptake of 99mTc-MDP in muscle than healthy age-matched controls

99mTc-MDP is an in vivo bone imaging agent that has been shown to highlight the inflammatory process and bone and muscle calcification in a wide range of osseous and non-osseous disorders. Histological studies of muscle from C57BL/10ScSn-Dmdmdx (MDX) mice have found degenerative lesions with calcification. The objective of this study was to image calcified lesions with 99mTc-MDP in a mouse model of muscular dystrophy. Subjects included male MDX mice (n=5) and controls (n=5). Mice were administered 99mTc-MDP intravenously (~700 µCi/animal) while awake and were allowed to be freely moving after tracer . Mice were anesthetized with isoflurane just prior to imaging and for the duration of each scan and were imaged on the nanoSPECT/CT (Mediso, Budapest, Hungary).  A 1x20min static whole-body SPECT scan was acquired followed by CT at 2 hours after tracer injection. Mice were imaged at 6, 15, and 19 weeks of age. After the final in vivo imaging timepoint, animals were euthanized, perfused and imaged post-life at ~3 hours post injection. Following post-life imaging, the diaphragm was resected from each animal, fixed in a formalin gel, and imaged ex vivo with SPECT/CT. Regions of interest were defined for the scapular muscles, heart, kidneys, quadriceps, skeleton, and diaphragm. Concentration (in SUV) of 99mTc-MDP in these regions was compared between groups at different time points.  At all imaging timepoints, 99mTc-MDP concentrations in the heart, left and right quadriceps were significantly (p<0.05) higher in MDX mice than controls. 99mTc-MDP concentrations in the left and right scapular muscles were also higher in MDX mice than control but only significantly higher in the right scapular at 6 weeks and left and right scapular at 15 weeks.  Post-life imaging was consistent with in vivo imaging at the week 16 timepoint. In ex vivo diaphragm imaging, 99mTc-MDP signal was noticeably higher in the diaphragms from MDX mice. The MDX mouse model of Duchenne Muscular Dystrophy shows greater uptake of 99mTc-MDP in muscle, particularly the quadriceps and diaphragm, as compared with controls. This agrees with histological reports of muscle calcification in MDX mice, and suggests that 99mTc-MDP could be a useful imaging assay in Muscular Dystrophy.

Carolynn M. Gaut, Jenna M, Sullivan, Whitney Woodson, Andrew W. Novicki, Edward J. Soares, Andy Sweet, Molly J Leen, Mark Lane, Dustin Kentala, Jacob Hesterman, Jack Hoppin, Ajay Verma

Please contact us at info@invicro.com for access to this poster.


Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis.

Datta G, Violante IR, Scott G, Zimmerman K, Santos-Ribeiro A, Rabiner EA, Gunn RN, Malik O, Ciccarelli O, Nicholas R, Matthews PM.
Mult Scler. 2016 Nov 30. pii: 1352458516681504. [Epub ahead of print]
PMID: 27903933

Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions.

Bishop CA, Newbould RD, Lee JS, Honeyfield L, Quest R, Colasanti A, Ali R, Mattoscio M, Cortese A, Nicholas R, Matthews PM, Muraro PA, Waldman AD.
Neuroimage Clin. 2016 Nov 9;13:9-15.

Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohn’s Disease.

Russo EA, Khan S, Janisch R, Gunn RN, Rabiner EA, Taylor SA, Matthews PM, Orchard TR.
Inflamm Bowel Dis. 2016 Nov;22(11):2619-2629.

Sleep problems and hypothalamic dopamine D3 receptor availability in Parkinson disease.

Pagano G, Molloy S, Bain PG, Rabiner EA, Chaudhuri KR, Brooks DJ, Pavese N.
Neurology. 2016 Nov 2. pii: 10.1212/WNL.0000000000003396. [Epub ahead of print]

Altered PDE10A expression detectable early before symptomatic onset in Huntington’s disease.

Niccolini F, Haider S, Reis Marques T, Muhlert N, Tziortzi AC, Searle GE, Natesan S, Piccini P, Kapur S, Rabiner EA, Gunn RN, Tabrizi SJ, Politis M.
Brain. 2015 Oct;138(Pt 10):3016-29. doi: 10.1093/brain/awv214. Epub 2015 Jul 21.

Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity.

Mick I, Ramos AC, Myers J, Stokes PR, Chandrasekera S, Erritzoe D, Mendez MA, Gunn RN, Rabiner EA, Searle GE, Galduróz JC, Waldman AD, Bowden-Jones H, Clark L, Nutt DJ, Lingford-Hughes AR.
Addict Biol. 2016 Oct 13. doi: 10.1111/adb.12457. [Epub ahead of print]

Opportunities and considerations for visualising neuroimaging data on very large displays.

Wall MB, Birch D, Yong MY.
F1000Res. 2016 Sep 2;5:2157. eCollection 2016.

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.

McGonigle J, Murphy A, Paterson LM, Reed LJ, Nestor L, Nash J, Elliott R, Ersche KD, Flechais RS, Newbould R, Orban C, Smith DG, Taylor EM, Waldman AD, Robbins TW, Deakin JW, Nutt DJ, Lingford-Hughes AR, Suckling J; ICCAM Platform.
J Psychopharmacol. 2016 Oct 4. pii: 0269881116668592. [Epub ahead of print]

Acute naltrexone does not remediate fronto-striatal disturbances in alcoholic and alcoholic polysubstance-dependent populations during a monetary incentive delay task.

Nestor LJ, Murphy A, McGonigle J, Orban C, Reed L, Taylor E, Flechais R, Paterson LM, Smith D, Bullmore ET, Ersche KD, Suckling J, Tait R, Elliott R, Deakin B, Rabiner I, Lingford-Hughes A, Nutt DJ, Sahakian B, Robbins TW; ICCAM Consortium.
Addict Biol. 2016 Sep 6. doi: 10.1111/adb.12444. [Epub ahead of print]

Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy.

Mankodi A, Bishop CA, Auh S, Newbould RD, Fischbeck KH, Janiczek RL.
Neuromuscul Disord. 2016 Oct;26(10):650-658. doi: 10.1016/j.nmd.2016.07.013. Epub 2016 Jul 28.

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational‘ hypotheses.

Lawn W, Freeman TP, Pope RA, Joye A, Harvey L, Hindocha C, Mokrysz C, Moss A, Wall MB, Bloomfield MA, Das RK, Morgan CJ, Nutt DJ, Curran HV.
Psychopharmacology (Berl). 2016 Oct;233(19-20):3537-52. doi: 10.1007/s00213-016-4383-x. Epub 2016 Sep 2.

Evidence of brain inflammation in patients with Human T Lymphotropic Virus type 1 associated myelopathy (HAM): A pilot multi modal imaging study using [11C] PBR28 PET, MR T1w and DWI.

Dimber R, Guo Q, Bishop C, Adonis A, Buckley A, Kocsis A, Owen D, Kalk N, Newbould R, Gunn R, Rabiner E, Taylor GP.
J Nucl Med. 2016 Aug 25. pii: jnumed.116.175083. [Epub ahead of print]

Loss of extra-striatal phosphodiesterase 10A expression in early premanifest Huntington’s disease gene carriers.

Wilson H, Niccolini F, Haider S, Marques TR, Pagano G, Coello C, Natesan S, Kapur S, Rabiner EA, Gunn RN, Tabrizi SJ, Politis M.
J Neurol Sci. 2016 Sep 15;368:243-8. doi: 10.1016/j.jns.2016.07.033. Epub 2016 Jul 15.

A Comparison of Magnetization Transfer Methods to Assess Brain and Cervical Cord Microstructure in Multiple Sclerosis.

Lema A, Bishop C, Malik O, Mattoscio M, Ali R, Nicholas R, Muraro PA, Matthews PM, Waldman AD, Newbould RD.
J Neuroimaging. 2016 Aug 5. doi: 10.1111/jon.12377. [Epub ahead of print]

Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in duchenne muscular dystrophy

Ami Mankodi, Courtney A. Bishop, Sungyoung Auh, Rexford D. Newbould, Kenneth H. Fischbeck, Robert Janiczek
Neuromuscular Disorders, Published Online:July 29, 2016 DOI: http://dx.doi.org/10.1016/j.nmd.2016.07.013

Quantification of [11C]Ro15-4513 GABAAα5 specific binding and regional selectivity in humans

Jim FM Myers, Robert A Comley, and Roger N Gunn
J Cereb Blood Flow Metab 0271678X16661339, first published on July 27, 2016 as doi:10.1177/0271678X16661339

Investigation of the Brain Biodistribution of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitor [18F]GSK2647544 in Healthy Male Subjects.

Huiban M, Coello C, Wu K, Xu Y, Lewis Y, Brown AP, Buraglio M, Guan C, Shabbir S, Fong R, Passchier J, Rabiner EA, Lockhart A.
Mol Imaging Biol. 2016 Jul 11. [Epub ahead of print]
PMID: 27402093 [PubMed – as supplied by publisher]

Clinical Translation of a ‘Click’ Labeled 18F-Octreotate Radioligand for Imaging Neuroendocrine Tumors.

Dubash SR, Keat N, Mapelli P, Twyman F, Carroll L, Kozlowski K, Al-Nahhas A Professor, Saleem A, Huiban M, Janisch R, Frilling A Professor, Sharma R, Aboagye E.
J Nucl Med. 2016 May 12;. [Epub ahead of print]
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LSD modulates music-induced imagery via changes in parahippocampal connectivity.

Kaelen M, Roseman L, Kahan J, Santos-Ribeiro A, Orban C, Lorenz R, Barrett FS, Bolstridge M, Williams T, Williams L, Wall MB, Feilding A, Muthukumaraswamy S, Nutt DJ, Carhart-Harris R.
Eur Neuropsychopharmacol. 2016 Apr 12;. [Epub ahead of print]
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In vivo imaging of microglial activation by positron emission tomography with [11 C]PBR28 in the 5XFAD model of Alzheimer’s disease.

Mirzaei N, Tang SP, Ashworth S, Coello C, Plisson C, Passchier J, Selvaraj V, Tyacke RJ, Nutt DJ, Sastre M.
Glia. 2016 Mar 9;. [Epub ahead of print]
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Neuroinflammation in treated HIV-positive individuals: A TSPO PET study.

Vera JH, Guo Q, Cole JH, Boasso A, Greathead L, Kelleher P, Rabiner EA, Kalk N, Bishop C, Gunn RN, Matthews PM, Winston A.
Neurology. 2016 Feb 24;. [Epub ahead of print]
PMID: 26911637 [PubMed – as supplied by publisher]

Phosphodiesterase 10A in Schizophrenia: A PET Study Using [11C]IMA107.

Marques TR, Natesan S, Niccolini F, Politis M, Gunn RN, Searle GE, Howes O, Rabiner EA, Kapur S.
Am J Psychiatry. 2016 Feb 19:appiajp201515040518. [Epub ahead of print]
PMID: 26892941

Magnetic resonance imaging reveals the complementary effects of decongestant and Breathe Right Nasal Strips on internal nasal anatomy.

Bishop CA, Johnson SM, Wall MB, Janiczek RL, Shanga G, Wise RG, Newbould RD, Murphy PS.
Laryngoscope. 2016 Feb 10. doi: 10.1002/lary.25906. [Epub ahead of print]
PMID: 26865420

Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.

Salem V, Izzi-Engbeaya C, Coello C, Thomas DB, Chambers ES, Comninos AN, Buckley A, Win Z, Al-Nahhas A, Rabiner EA, Gunn RN, Budge H, Symonds ME, Bloom SR, Tan TM, Dhillo WS.
Diabetes Obes Metab. 2016 Jan;18(1):72-81. doi: 10.1111/dom.12585. Epub 2015 Nov 20.
PMID: 26434748


A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway.

Cheraghchi-Bashi A, Parker CA, Curry E, Salazar JF, Gungor H, Saleem A, Cunnea P, Rama N, Salinas C, Mills GB, Morris SR, Kumar R, Gabra H, Stronach EA.
Oncotarget. 2015 Dec 8;6(39):41736-49. doi: 10.18632/oncotarget.6153.

Hippocampal Neuroinflammation, Functional Connectivity, and Depressive Symptoms in Multiple Sclerosis.

Colasanti A, Guo Q, Giannetti P, Wall MB, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PA, Malik O, Owen DR, Young AH, Gunn RN, Piccini P, Matthews PM, Rabiner EA
Biol Psychiatry. 2015 Dec 5;. [Epub ahead of print]
PMID: 26809249 [PubMed – as supplied by publisher]

18F-FLT PET imaging of cellular proliferation in pancreatic cancer.

Lamarca A, Asselin MC, Manoharan P, McNamara MG, Trigonis I, Hubner R, Saleem A, Valle JW.
Crit Rev Oncol Hematol. 2015 Dec 29;. [Epub ahead of print]
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Neural Systems Involved When Attending to a Speaker.

Kamourieh S, Braga RM, Leech R, Newbould RD, Malhotra P, Wise RJ.
Cereb Cortex. 2015 Nov;25(11):4284-98. doi: 10.1093/cercor/bhu325. Epub 2015 Jan 16.
PMID: 25596592

Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers.

Mick I, Myers J, Ramos AC, Stokes PR, Erritzoe D, Colasanti A, Gunn RN, Rabiner EA, Searle GE, Waldman AD, Parkin MC, Brailsford AD, Galduróz JC, Bowden-Jones H, Clark L, Nutt DJ, Lingford-Hughes AR.

Neuropsychopharmacology. 2015 Nov 10;. [Epub ahead of print]
PMID: 26552847 [PubMed – as supplied by publisher]

Quantitative imaging of protein targets in the human brain with PET.

Gunn RN, Slifstein M, Searle GE, Price JC.
Phys Med Biol. 2015 Oct 29;60(22):R363-R411. [Epub ahead of print]
PMID: 26513176 [PubMed – as supplied by publisher]

Impact of image-based motion correction on dopamine D3/D2 receptor occupancy-comparison of groupwise and frame-by-frame registration approaches.

Jiao J, Searle GE, Schnabel JA, Gunn RN.
EJNMMI Phys. 2015 Dec;2(1):15.
PMID: 26501816 [PubMed]

Glucagon Increases Energy Expenditure Independently of Brown Adipose Tissue Activation in Humans.

Salem V, Izzi-Engbeaya C, Coello C, Thomas DB, Chambers ES, Comninos A, Buckley A, Win Z, Al-Nahhas A, Rabiner EA, Gunn RN, Bloom SR, Tan TM, Dhillo WS.
Diabetes Obes Metab. 2015 Oct 5;. [Epub ahead of print]
PMID: 26434748 [PubMed – as supplied by publisher]

Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson’s disease.

Niccolini F, Foltynie T, Reis Marques T, Muhlert N, Tziortzi AC, Searle GE, Natesan S, Kapur S, Rabiner EA, Gunn RN, Piccini P, Politis M.
Brain. 2015 Oct;138(Pt 10):3003-15. doi: 10.1093/brain/awv219. Epub 2015 Jul 25.
PMID: 26210536

Altered PDE10A expression detectable early before symptomatic onset in Huntington’s disease.

Niccolini F, Haider S, Reis Marques T, Muhlert N, Tziortzi AC, Searle GE, Natesan S, Piccini P, Kapur S, Rabiner EA, Gunn RN, Tabrizi SJ, Politis M.
Brain. 2015 Oct;138(Pt 10):3016-29. doi: 10.1093/brain/awv214. Epub 2015 Jul 21.
PMID: 26198591

Dose-finding quantitative FDG PET imaging study with the oral pan-AKT inhibitor GSK2141795 in patients with gynecological malignancies.

Gungor H, Saleem A, Babar S, Dina R, El-Bahrawy M, Curry E, Rama N, Chen M, Pickford E, Agarwal R, Blagden S, Carme S, Salinas C, Madison SJ, Krachey EC, Santiago-Walker A, Smith DA, Morris SR, Stronach EA, Gabra H.
J Nucl Med. 2015 Oct 1;. [Epub ahead of print]
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Human kinetic modelling of the 5-HT6 PET radioligand, 11C-GSK215083, and its utility for determining occupancy at both 5HT6 and 5HT2A receptors by SB742457 as a potential therapeutic mechanism of action in Alzheimer’s disease.

Parker CA, Rabiner EI, Gunn R, Searle G, Martarello L, Comley R, Davy M, Wilson AA, Houle S, Mizrahi R, Laruelle M, Cunningham VJ.
J Nucl Med. 2015 Sep 17;. [Epub ahead of print]
PMID: 26383152 [PubMed – as supplied by publisher

The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

Paterson LM, Flechais RS, Murphy A, Reed LJ, Abbott S, Boyapati V, Elliott R, Erritzoe D, Ersche KD, Faluyi Y, Faravelli L, Fernandez-Egea E, Kalk NJ, Kuchibatla SS, McGonigle J, Metastasio A, Mick I, Nestor L, Orban C, Passetti F, Rabiner EA, Smith DG, Suckling J, Tait R, Taylor EM, Waldman AD, Robbins TW, Deakin JW, Nutt DJ, Lingford-Hughes AR.
J Psychopharmacol. 2015 Aug 5;. [Epub ahead of print]
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Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer

Saleem, Azeem;  Searle, Graham E.;  Kenny, Laura M.;  Huiban, Mickael;  Kozlowski, Kasia et al. (2015)
EJNMMI Research vol. 5 (1)

Carbon-11 radiolabelling of organosulfur compounds: (11) C synthesis of the progesterone receptor agonist tanaproget.

Haywood T, Kealey S, Sánchez-Cabezas S, Hall JJ, Allott L, Smith G, Plisson C, Miller PW.
Chemistry. 2015 Jun 15;21(25):9034-8. doi: 10.1002/chem.201501089. Epub 2015 May 12.
PMID: 25965348

Further evaluation of [11C]MP-10 as a radiotracer for phosphodiesterase 10A: PET imaging study in rhesus monkeys and brain tissue metabolite analysis

Lin, Shu Fei;  Labaree, David;  Chen, Ming Kai;  Holden, Daniel;  Gallezot, Jean Dominique et al. (2015)
Synapse vol. 69 (2) p. 86-95

phMRI: methodological considerations for mitigating potential confounding factors.

Bourke JH, Wall MB.
Front Neurosci. 2015 May 7;9:167. doi: 10.3389/fnins.2015.00167. eCollection 2015. Review.
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The simplified reference tissue model: Model assumption violations and their impact on binding potential

Salinas, Cristian A.;  Searle, Graham E.;  Gunn, Roger N. (2015)
Journal of Cerebral Blood Flow and Metabolism vol. 35 (2) p. 304-311

In vivo occupancy of the 5-HT1A receptor by a novel pan 5-HT1(A/B/D) receptor antagonist, GSK588045, using positron emission tomography

Comley, Robert A.;  Van Der Aart, Jasper;  Gulyás, Balázs;  Garnier, Martine;  Iavarone, Laura et al. (2015)
Neuropharmacology vol. 92 p. 44-48

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.

Sami MB, Rabiner EA, Bhattacharyya S.
Eur Neuropsychopharmacol. 2015 Aug;25(8):1201-24. doi: 10.1016/j.euroneuro.2015.03.011. Epub 2015 Mar 30.
PMID: 26068702

A dual radiolabelling approach for tracking metal complexes: Investigating the speciation of copper bis(thiosemicarbazonates) in vitro and in vivo

Hueting, Rebekka;  Kersemans, Veerle;  Tredwell, Matthew;  Cornelissen, Bart;  Christlieb, Martin et al. (2015)
Metallomics vol. 7 (5) p. 795-804

Neural Systems Involved When Attending to a Speaker.

Cereb Cortex. 2015 Jan 16. pii: bhu325. [Epub ahead of print]


An evaluation of the brain distribution of [ 11 C]GSK1034702, a muscarinic-1 (M 1) positive allosteric modulator in the living human brain using positron emission tomography.

EJNMMI Research 2014, 4:66

In vivo occupancy of the 5-HT1A receptor by a novel pan 5-HT1(A/B/D) receptor antagonist, GSK588045, using positron emission tomography.

2014 Dec 2. pii: S0028-3908(14)00433-X. doi: 10.1016/j.neuropharm.2014.11.017. [Epub ahead of print]

The simplified reference tissue model: model assumption violations and their impact on binding potential.

J Cereb Blood Flow Metab. 2014 Nov 26. doi: 10.1038/jcbfm.2014.202. [Epub ahead of print]

Why Are We Failing to Implement Imaging Studies with Radiolabelled New Molecular Entities in Early Oncology Drug Development?

The Scientific World Journal Volume 2014 (2014), Article ID 269605

Henry Wagner Best Paper Award – SNMMI, St Louis, USA, June 2014

PET brain imaging reveals first signs of Huntington’s up to 30 years before onset.
BRC-funded study by London researchers and Imanova could lead to new disease progression blocking treatments.

Brain phosphodiesterase 10A (PDE-10A) density in early premanifest HD gene carriers.

J Nuclear Medicine 55 (Supplement 1):32.)

Effects of ecstasy on cooperative behaviour and perception of trustworthiness: A naturalistic study

J Psychopharmacol. 2014 Aug 13. pii: 0269881114544775.

Dopamine D3 receptor ligands for drug addiction treatment: update on recent findings

Prog Brain Res. 2014;211:255-75. doi: 10.1016/B978-0-444-63425-2.00011-8.

In vivo assessment of brain white matter inflammation in Multiple Sclerosis with 18F-PBR111 PET

J Nucl Med. 2014 Jun 5. pii: jnumed.113.135129.

Amphetamine induced endogenous opioid release in the human brain detected with [11C]carfentanil PET: replication in an independent cohort

Int J Neuropsychopharmacol. 2014 May 7:1-6.

Connectivity-based functional analysis of dopamine release in the striatum using diffusion-weighted MRI and positron emission tomography

Cereb Cortex. 2014 May;24(5):1165-77. doi: 10.1093/cercor/bhs397.

Phosphodiesterase 10A PET radioligand development program: from pig to human

J Nucl Med. 2014 Apr;55(4):595-601. doi: 10.2967/jnumed.113.131409.

Central 5-HT4 receptor binding as biomarker of serotonergic tonus in humans: a [11C]SB207145 PET study

Mol Psychiatry. 2014 Apr;19(4):427-32. doi: 10.1038/mp.2013.147.

The effect of acutely administered MDMA on subjective and BOLD-fMRI responses to favourite and worst autobiographical memories

Int J Neuropsychopharmacol. 2014 Apr;17(4):527-40. doi: 10.1017/S1461145713001405.

Palladium-mediated oxidative carbonylation reactions for the synthesis of (11) C-radiolabelled ureas

J Labelled Comp Radiopharm. 2014 Apr;57(4):202-8. doi: 10.1002/jlcr.3151.

A graphical method to compare the in vivo binding potential of PET radioligands in the absence of a reference region: application to [11C]PBR28 and [18F]PBR111 for TSPO imaging

J Cereb Blood Flow Metab. 2014 Apr 16. doi: 10.1038/jcbfm.2014.65.

Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [(11)C]MP-10 PET rodent imaging study with ex vivo confirmation

Transl Psychiatry. 2014 Apr 1;4:e376. doi: 10.1038/tp.2014.17.

Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis

Neuroimage Clin. 2014 Mar 31;4:641-8. doi: 10.1016/j.nicl.2014.02.004.

Imaging nicotine- and amphetamine-induced dopamine release in rhesus monkeys with [(11)C]PHNO vs [(11)C]raclopride PET

Neuropsychopharmacology. 2014 Mar;39(4):866-74. doi: 10.1038/npp.2013.286.

Unexpectedly high affinity of a novel histamine H(3) receptor antagonist, GSK239512, in vivo in human brain, determined using PET

Br J Pharmacol. 2014 Mar;171(5):1241-9. doi: 10.1111/bph.12505.

Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

J Cereb Blood Flow Metab. 2014 Mar 19. doi: 10.1038/jcbfm.2014.46.

Characterising the plasma-target occupancy relationship of the neurokinin antagonist GSK1144814 with PET

J Psychopharmacol. 2014 Mar;28(3):244-53. doi: 10.1177/0269881113517953.

Relationship between glycine transporter 1 inhibition as measured with Positron Emission Tomography and changes in cognitive performances in non-human primates

Neuropsychopharmacology. 2014 Feb 3. doi: 10.1038/npp.2014.4.

Phase II trial of Cetuximab and conformal radiotherapy only in locally advanced pancreatic cancer with concurrent tissue sampling feasibility study

Transl Oncol. 2014 Feb 1;7(1):55-64. eCollection 2014.

The effects of acutely administered 3,4-Methylenedioxymethamphetamine on spontaneous brain function in healthy volunteers measured with arterial spin labeling and blood oxygen level-dependent resting state functional connectivity

Biol Psychiatry. 2014 Jan 10. pii: S0006-3223(14)00005-5. doi: 10.1016/j.biopsych.2013.12.015.

A comparison of the behavior of (64)Cu-acetate and (64)Cu-ATSM in vitro and in vivo

J Nucl Med. 2014 Jan;55(1):128-34. doi: 10.2967/jnumed.113.119917.

Spatio-temporal pharmacokinetic model based registration of 4D PET neuroimaging data

Neuroimage. 2014 Jan 1;84:225-35. doi: 10.1016/j.neuroimage.2013.08.031.

Making drug development visible – and viable

Drug Discov Today. 2014 Jan;19(1):1-3. doi: 10.1016/j.drudis.2013.10.007.


In vivo imaging of cerebral dopamine D3 receptors in alcoholism

Neuropsychopharmacology. 2014 Jan 28. doi: 10.1038/npp.2014.18.

Translational PET imaging research

Neurobiol Dis. 2014 Jan;61:32-8. doi: 10.1016/j.nbd.2013.08.017.


Negishi coupling reactions as a valuable tool for [11C]methyl-arene formation; first proof of principle

Chem Commun (Camb). 2013 Dec 14;49(96):11326-8. doi: 10.1039/c3cc47203e.

Are prescribed benzodiazepines likely to affect the availability of the 18 kDa translocator protein (TSPO) in PET studies?

Synapse. 2013 Dec;67(12):909-12. doi: 10.1002/syn.21681.

Unexpected high affinity of a novel H3 receptor antagonist, GSK239512, in vivo in human brain, determined using positron emission tomography (PET)

British Journal of Pharmacology. 2013. doi: 10.1111/bph.12505.

PET neuroimaging: the elephant unpacks his trunk: comment on Cumming: “PET neuroimaging: the white elephant packs his trunk?”

Neuroimage. 2013 Dec 31. doi: 10.1016/j.neuroimage.2013.12.042.

Quantification of the specific translocator protein signal of 18F-PBR111 in healthy humans: a genetic polymorphism effect on in vivo binding

J Nucl Med. 2013 Nov;54(11):1915-23. doi: 10.2967/jnumed.113.121020.

Resting state synchrony in anxiety-related circuits of abstinent alcohol-dependent patients

Am J Drug Alcohol Abuse. 2013 Nov;39(6):433-40. doi: 10.3109/00952990.2013.846348.

Awake non-human primate brain PET imaging with minimal head restraint: evaluation of GABAA-benzodiazepine binding with 11C-flumazenil in awake and anesthetized animals

J Nucl Med. 2013 Nov;54(11):1962-8. doi: 10.2967/jnumed.113.122077.

A broadly applicable [18F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging

Nat Chem. 2013 Nov;5(11):941-4. doi: 10.1038/nchem.1756.

Bipolar disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa translocator protein (TSPO)

Psychoneuroendocrinology. 2013 Nov;38(11):2826-9. doi: 10.1016/j.psyneuen.2013.07.007.

Technologies: preclinical imaging for drug development

Drug Discov Today Technol. 2013 Sep;10(3):e343-50. doi: 10.1016/j.ddtec.2012.04.004.

A 3 T sodium and proton composite array breast coil

Magn Reson Med. 2013 Sep 16. doi: 10.1002/mrm.24860.

Monoamine transporter occupancy of a novel triple reuptake inhibitor in baboons and humans using positron emission tomography

J Pharmacol Exp Ther. 2013 Aug;346(2):311-7. doi: 10.1124/jpet.112.202895.

T1-weighted sodium MRI of the articulator cartilage in osteoarthritis: a cross sectional and longitudinal study

PLoS One. 2013 Aug 5;8(8):e73067. doi: 10.1371/journal.pone.0073067.

Non linear mixed effects analysis in PET PK-receptor occupancy studies

Neuroimage. 2013 Aug 1;76:155-66. doi: 10.1016/j.neuroimage.2013.03.006.

Catalytic decarboxylative fluorination for the synthesis of tri- and difluoromethyl arenes

Org Lett. 2013 Jun 7;15(11):2648-51. doi: 10.1021/ol4009377.

Kinetic analysis of drug-target interactions with PET for characterization of pharmacological hysteresis

J Cereb Blood Flow Metab. 2013 May;33(5):700-7. doi: 10.1038/jcbfm.2012.208.

Use of LC-MS for the quality control of radiopharmaceuticals: example of [(18)F]ML10

J Labelled Comp Radiopharm. 2013 May 30;56(6):330-3. doi: 10.1002/jlcr.3023.

Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies

J Psychopharmacol. 2013 May;27(5):424-34. doi: 10.1177/0269881113480990.

Mathematical modelling of [¹¹C]-(+)-PHNO human competition studies

Neuroimage. 2013 Mar;68:119-32. doi: 10.1016/j.neuroimage.2012.11.033.

A non-linear mixed effect modelling approach for metabolite correction of the arterial input function in PET studies.

Veronese M, Gunn RN, Zamuner S, Bertoldo A.
Neuroimage. 2013 Feb 1;66:611-22. doi: 10.1016/j.neuroimage.2012.10.048. Epub 2012 Oct 27.
PMID: 23108277

A generalised spatio-temporal registration framework for dynamic PET data: application to neuroreceptor imaging

Med Image Comput Comput Assist Interv. 2013;16(Pt 1):211-8.

Occupancy of brain dopamine D3 receptors and drug craving: a translational approach

Neuropsychopharmacology. 2013 Jan;38(2):302-12. doi: 10.1038/npp.2012.171.


Orbitofrontal connectivity with resting-state networks is associated with midbrain dopamine D3 receptor availability

Cereb Cortex. 2012 Dec;22(12):2784-93. doi: 10.1093/cercor/bhr354.

A non-linear mixed effect modelling approach for metabolite correction of the arterial input function in PET studies

Neuroimage. 2012 Oct 27;66C:611-622. doi: 10.1016/j.neuroimage.2012.10.048.

Endogenous opioid release in the human brain reward system induced by acute amphetamine administration

Biol Psychiatry. 2012 Sep 1;72(5):371-7. doi: 10.1016/j.biopsych.2012.01.027.

Biodistribution and radiation dosimetry of the serotonin 5-HT6 ligand [11C]GSK215083 determined from human whole-body PET

Mol Imaging Biol. 2012 Aug;14(4):517-521. doi: 10.1007/s11307-011-0523-1.

The development, past achievements, and future directions of brain PET

J Cereb Blood Flow Metab. 2012 Jul;32(7):1426-54. doi: 10.1038/jcbfm.2012.20.

Metal-free oxidative fluorination of phenols with [18F]fluoride

Angew Chem Int Ed Engl. 2012 Jul 2;51(27):6733-7. doi: 10.1002/anie.201201502.

Affinity and selectivity of [¹¹C]-(+)-PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo

Synapse. 2012 Jun;66(6):489-500. doi: 10.1002/syn.21535.

Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs

J Cereb Blood Flow Metab. 2012 May;32(5):874-83. doi: 10.1038/jcbfm.2012.1.

In vivo dopaminergic and behavioral responses to acute cocaine are altered in adenosine A(2A) receptor knockout mice

Synapse. 2012 May;66(5):383-90. doi: 10.1002/syn.21527.

Identifying improved TSPO PET imaging probes through biomathematics: the impact of multiple TSPO binding sites in vivo

Neuroimage. 2012 Apr 2;60(2):902-10. doi: 10.1016/j.neuroimage.2011.12.078.

Dynamic, adaptive changes in MAO-A binding after alterations in substrate availability: an in vivo [11C]-harmine positron emission tomography study

J Cereb Blood Flow Metab. Mar 2012; 32(3): 443–446. doi: 10.1038/jcbfm.2011.184.

Positron emission tomography molecular imaging for drug development

Br J Clin Pharmacol. 2012 Feb;73(2):175-86. doi: 10.1111/j.1365-2125.2011.04085.x.

Automated preparation of the dopamine D2/3 receptor agonist ligand [11C]-(+)-PHNO for human PET imaging studies

Appl Radiat Isot. 2012 Feb;70(2):380-7. doi: 10.1016/j.apradiso.2011.09.018.

Radiosynthesis and characterization of 11C-GSK215083 as a PET radioligand for the 5-HT6 receptor

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Radiation dose estimates for carbon-11-labelled PET tracers

Nucl Med Biol. 2012 Feb;39(2):305-14. doi: 10.1016/j.nucmedbio.2011.08.005.

A pharmacokinetic PET study of NK₁ receptor occupancy

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Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity to acute amphetamine challenge in healthy humans

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An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28

J Cereb Blood Flow Metab. 2012 Jan;32(1):1-5. doi: 10.1038/jcbfm.2011.147.

A pilot randomized, placebo controlled, double blind phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers

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MR-DTI and PET multimodal imaging of dopamine release within subdivisions of basal ganglia

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Translational characterization of [11C]GSK931145, a PET ligand for the glycine transporter type 1

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Characterization of in vivo pharmacological properties and sensitivity to endogenous serotonin of [11C] P943: a positron emission tomography study in papio anubis

Synapse. 2011 Nov;65(11):1119-27. doi: 10.1002/syn.20946.

The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans

Cell Metab. 2011 Nov 2;14(5):700-6. doi: 10.1016/j.cmet.2011.09.010.

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Simultaneous T₂ and lipid quantitation using IDEAL-CPMG

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Presynaptic 5-HT1A is related to 5-HTT receptor density in the human brain

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Fully automated synthesis of the M₁ receptor agonist [¹¹C]GSK1034702 for clinical use on an Eckert & Ziegler Modular Lab system

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Non-invasive imaging in experimental medicine for drug development

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Motion-sensitized driven equilibrium for blood-suppressed T2* mapping

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Molecular and functional neuroimaging of human opioid receptor pharmacology

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Biodistribution and radiation dosimetry of the glycine transporter-1 ligand 11C-GSK931145 determined from primate and human whole-body PET

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Radiosynthesis and in vivo evaluation of [(11)C]MP-10 as a positron emission tomography radioligand for phosphodiesterase 10A

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Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans

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Rapid carbonylative coupling reactions using palladium(I) dimers: applications to 11CO-radiolabelling for the synthesis of PET tracers

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Evaluation of dopamine D2/3 specific binding in the cerebellum for the PET radiotracer [11C]FLB 457: implications for measuring cortical dopamine release

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Prediction of repeat-dose occupancy from single-dose data: characterisation of the relationship between plasma pharmacokinetics and brain target occupancy

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Variation in binding affinity of the novel anxiolytic XBD173 for the 18 kDa translocator protein in human brain

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Evaluation of novel N1-methyl-2-phenylindol-3-ylglyoxylamides as a new chemotype of 18 kDa translocator protein-selective ligand suitable for the development of positron emission tomography radioligands

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Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy

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Mixed-affinity binding in humans with 18-kDa translocator protein ligands

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Three-dimensional T(1), T(2) and proton density mapping with inversion recovery balanced SSFP

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Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation

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Evaluation of 11C-GSK189254 as a novel radioligand for the H3 receptor in humans using PET

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Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade of the 5-HT 2A receptors

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Improvements in parallel imaging accelerated functional MRI using multiecho echo-planar imaging

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