11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than11C-( R)-PK11195.
Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent11C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the "signal to background" ratio (assessed as binding potential ( BPND)) of11C-( R)-PK11195 compared to one of the most promising second-generation radioligands,11C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either11C-( R)-PK11195 (16 subjects) or11C-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30-90 mg PO).11C-DPA-713 showed a significant sensitivity to genotype in brain, whereas11C-( R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of11C-DPA-713 was much greater than that of11C-( R)-PK11195. The BPNDin high-affinity binders was about 10-fold higher for11C-DPA-713 (7.3) than for11C-( R)-PK11195 (0.75). Although the high specific binding of11C-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Masato
M
Kobayashi
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Teresa
T
Jiang
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Sanjay
S
Telu
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Sami S
SS
Zoghbi
2 Imanova Ltd, London, UK.|3 Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
Roger N
RN
Gunn
2 Imanova Ltd, London, UK.
Eugenii A
EA
Rabiner
3 Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
David R
DR
Owen
2 Imanova Ltd, London, UK.
Qi
Q
Guo
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Victor W
VW
Pike
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Robert B
RB
Innis
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Masahiro
M
Fujita
D000081:Acetamides / Q000493:pharmacokinetics*; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes; D002536:Cerebral Arteries / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011687:Purines / Q000494:pharmacology; D011720:Pyrazoles / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D018079:Receptors, GABA / Q000235:genetics* / Q000378:metabolism*
D000081:Acetamides; D002250:Carbon Radioisotopes; C000615233:Carbon-11; D007546:Isoquinolines; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; C502525:N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195
18 kDa (TSPO); XBD173; metabolite-corrected arterial input; positron emission tomography; rs6971 polymorphism