Radiation Dosimetry and Biodistribution in Monkey and Man of 11C-PBR28: A PET Radioligand to Image Inflammation

Brown, Amira K.; Fujita, Masahiro; Fujimura, Yota; Liow, Jeih‐San; Stabin, Michael G.; Ryu, Young Hoon; Imaizumi, Masao; Hong, Jinsoo; Pike, Victor W.; Innis, Robert B.

doi:10.2967/jnumed.107.044842

Cited by 137 publications

(105 citation statements)

References 14 publications

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“…The biodistribution and dosimetry of other PBR radioligands has been performed previously in animals (9, 18-23) and healthy adult human volunteers (16,18,24). Hashimoto et al (21) studied the biodistribution of 3 H-PK 11195 in mice and found high accumulations of radioactivity in the heart, lung, spleen, kidneys, and adrenals.…”

Section: Discussionmentioning

confidence: 99%

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

Kumar¹,

Muzik²,

Chugani³

et al. 2009

J Nucl Med

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The PET tracer 11 C-(R)-PK11195 (PK) is an antagonist of the peripheral-type benzodiazepine binding site and allows the noninvasive imaging of microglial activation seen in several neurologic disorders affecting the mature and developing brain. The objective of this study was to derive the biodistribution and in vivo radiation dose estimates of PK in children studied for brain inflammatory conditions and in healthy adults. Methods: Twenty-two children (mean age 6 SD, 9.5 6 4 y; range, 4-17 y; 10 girls) who underwent dynamic PK PET for conditions involving brain inflammation were studied. Seven healthy adults (age, 27.4 6 7.5 y; range, 22-41 y; 3 women) were evaluated using the same protocol. Normal-organ time-activity curves and residence times were derived and absorbed doses then calculated using the OLINDA software. Two other healthy young adults (1 man, 1 woman) also underwent sequential whole-body PET using a PET/CT scanner to obtain corresponding CT images and PK pharmacokinetics. Results: PK uptake was highest in the gallbladder and urinary bladder, followed by the liver, kidney, bone marrow, salivary gland, and heart wall, with minimal localization in all other organs including normal brain and lungs. PK was excreted through the hepatobiliary and renal systems. The average effective dose equivalent was 11.6 6 0.6 mSv/MBq (mean 6 SD) for young children (age, 4-7 y), 7.7 6 1.0 mSv/ MBq for older children (age, 8-12 y), 5.3 6 0.5 mSv/MBq for adolescents (age, 13-17 y), and 4.6 6 2.7 mSv/MBq for adults. The gallbladder wall received the highest radiation dose in children younger than 12 y, whereas the urinary bladder wall received the highest dose in older children and adults. For an administered activity of 17 MBq/kg (0.45 mCi/kg), the effective dose equivalent was about 5 mSv or below for all age groups. Conclusion: At clinically practical administered activities, the radiation dose from 11 C-PK11195 in both children and adults is comparable to that from other clinical PET tracers and diagnostic radiopharmaceuticals in routine clinical use.

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Section: Discussionmentioning

confidence: 99%

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

Kumar¹,

Muzik²,

Chugani³

et al. 2009

J Nucl Med

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“…Multiple attempts have been made in recent years to develop a radiotracer with higher affinity to PBRs than PK11195 (Zhang et al, 2003;Fujimura et al, 2006;Brown et al, 2007). Higher affinity suggested by the differences in dissociation constants may address some of the issues related to nonspecific binding reported with PK11195.…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation Extends Brain Tissue at Risk to Vital Peri-Infarct Tissue: A Double Tracer [¹¹C]PK11195- and [¹⁸F]FDG-PET Study

Schroeter

Dennin

Walberer

et al. 2009

J Cereb Blood Flow Metab

113

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Focal cerebral ischemia elicits strong inflammatory responses involving activation of resident microglia and recruitment of monocytes/macrophages. These cells express peripheral benzodiazepine receptors (PBRs) and can be visualized by positron emission tomography (PET) using [ 11 C]PK11195 that selectively binds to PBRs. Earlier research suggests that transient ischemia in rats induces increased [11 C]PK11195 binding within the infarct core. In this study, we investigated the expression of PBRs during permanent ischemia in rats. Permanent cerebral ischemia was induced by injection of macrospheres into the middle cerebral artery. Multimodal imaging 7 days after ischemia comprised (1) 18 F]FDG metabolic rate constant with accumulated activated microglia and macrophages. These results suggest that after permanent focal ischemia, neuroinflammation occurring in the normoperfused peri-infarct zone goes along with increased energy demand, therefore extending the tissue at risk to areas adjacent to the infarct.

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“…Neuropathologic evidence has demonstrated that an increase in TSPO and concurrent microglial and astroglial activation accompanies the neurodegenerative process in Alzheimer disease (7)(8)(9). These findings motivated the development of imaging probes labeled by positron-emitting radionuclides and have enabled visualization of the distribution and change in TSPO induced by microglial activation in normal and abnormal brains of humans and animals (10)(11)(12)(13)(14)(15)(16)(17)(18). 11 C-labeled (R)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195) was the first PET ligand used for clinical imaging of TSPO (19).…”

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confidence: 99%

¹⁸F-FEAC and ¹⁸F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain

Yui¹,

Maeda²,

Kumata³

et al. 2010

J Nucl Med

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We evaluated two F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl] acetamide ( 18 F-FEAC) and N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-18 F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ( 18 F-FEDAC), by investigating their kinetics in the monkey brain and by performing in vitro and in vivo imaging of translocator protein (18 kDa) (TSPO) in the infarcted rat brain. Methods: Dissection was used to determine the distribution of 18 F-FEAC and 18 F-FEDAC in mice, whereas PET was used for a monkey. With each 18 F-ligand, in vitro autoradiography and small-animal PET were performed on infarcted rat brains. Results: 18 F-FEAC and 18 F-FEDAC had a high uptake of radioactivity in the heart, lung, and other TSPO-rich organs of mice. In vitro autoradiography showed that the binding of each 18 F-ligand significantly increased on the ipsilateral side of rat brains, compared with the contralateral side. In a smallanimal PET study, PET summation images showed the contrast of radioactivity between ipsilateral and contralateral sides. Pretreatment with TSPO ligands N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide (AC-5216) or (R)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195) diminished the difference in uptake between the 2 sides. The PET study showed that each 18 F-ligand had uptake and distribution patterns in the monkey brain similar to those of 11 C-AC-5216. After injection into the monkey during PET, the uptake of each 18 F-ligand in the brain decreased over time whereas 11 C-AC-5216 did not. In the brain homogenate of mice, the percentage of the fraction corresponding to intact 18 F-FEAC and 18 F-FEDAC was 68% and 75% at 30 min after injection. In monkey plasma, each 18 F-ligand was scarcely metabolized until the end of the PET scan. Conclusion: 18 F-FEAC and 18 F-FEDAC produced in vitro and in vivo signals allowing visualization of the increase in TSPO expression in the infarcted rat brain. The kinetics of both 18 F-ligands in the monkey brain and tolerance for in vivo metabolism suggested their usefulness for imaging studies of TSPO in primates.

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Radiation Dosimetry and Biodistribution in Monkey and Man of 11C-PBR28: A PET Radioligand to Image Inflammation

Cited by 137 publications

References 14 publications

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

Neuroinflammation Extends Brain Tissue at Risk to Vital Peri-Infarct Tissue: A Double Tracer [¹¹C]PK11195- and [¹⁸F]FDG-PET Study

¹⁸F-FEAC and ¹⁸F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain

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Radiation Dosimetry and Biodistribution in Monkey and Man of 11C-PBR28: A PET Radioligand to Image Inflammation

Cited by 137 publications

References 14 publications

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand 11C-(R)-PK11195 in Children and Adults

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand 11C-(R)-PK11195 in Children and Adults

Neuroinflammation Extends Brain Tissue at Risk to Vital Peri-Infarct Tissue: A Double Tracer [11C]PK11195- and [18F]FDG-PET Study

18F-FEAC and 18F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain

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PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

PET-Derived Biodistribution and Dosimetry of the Benzodiazepine Receptor-Binding Radioligand ¹¹C-(R)-PK11195 in Children and Adults

Neuroinflammation Extends Brain Tissue at Risk to Vital Peri-Infarct Tissue: A Double Tracer [¹¹C]PK11195- and [¹⁸F]FDG-PET Study

¹⁸F-FEAC and ¹⁸F-FEDAC: PET of the Monkey Brain and Imaging of Translocator Protein (18 kDa) in the Infarcted Rat Brain