TY - JOUR
T1 - Whole-body biodistribution kinetics, metabolism, and radiation dosimetry estimates of 18F-PEG6-IPQA in nonhuman primates
AU - Tian, Mei
AU - Ogawa, Kazuma
AU - Wendt, Richard
AU - Mukhopadhyay, Uday
AU - Balatoni, Julius
AU - Fukumitsu, Nobuyoshi
AU - Uthamanthil, Rajesh
AU - Borne, Agatha
AU - Brammer, David
AU - Jackson, James
AU - Mawlawi, Osama
AU - Yang, Bijun
AU - Alauddin, Mian M.
AU - Gelovani, Juri G.
PY - 2011/6/1
Y1 - 2011/6/1
N2 - We recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2- (2-[2-{2-(18F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]- quinazoline-6-yl-acrylamide) (18F-PEG6-IPQA) for noninvasive detection of active mutant epidermal growth factor receptor kinase-expressing non-small cell lung cancer xenografts in rodents. In this study, we determined the pharmacokinetics, biodistribution, metabolism, and radiation dosimetry of 18F-PEG6-IPQA in nonhuman primates. Methods: Six rhesus macaques were injected intravenously with 141 ± 59.2 MBq of 18F-PEG6-IPQA, and dynamic PET/CT images covering the thoracoabdominal area were acquired for 30 min, followed by whole-body static images at 60, 90, 120, and 180 min. Blood samples were obtained from each animal at several time points after radiotracer administration. Radiolabeled metabolites in blood and urine were analyzed using high-performance liquid chromatography. The 18F-PEG6-IPQA pharmacokinetic and radiation dosimetry estimates were determined using volume-of-interest analysis of PET/CT image datasets and blood and urine time-activity data. Results: 18F-PEG6-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. 18F-PEG 6 was the major radioactive metabolite. The critical organ was the gallbladder, with an average radiation-absorbed dose of 0.394 mSv/MBq. The other key organs with high radiation doses were the kidneys (0.0830 mSv/MBq), upper large intestine wall (0.0267 mSv/MBq), small intestine (0.0816 mSv/MBq), and liver (0.0429 mSv/MBq). Lung tissue exhibited low uptake of 18F- PEG6-IPQA due to the low affinity of this radiotracer to wild-type epidermal growth factor receptor kinase. The effective dose was 0.0165 mSv/MBq. No evidence of acute cardiotoxicity or of acute or delayed systemic toxicity was observed. On the basis of our estimates, diagnostic dosages of 18F-PEG6-IPQA up to 128 MBq (3.47 mCi) per injection should be safe for administration in the initial cohort of human patients in phase I clinical PET studies. Conclusion: The whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of 18F-PEG6-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.
AB - We recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2- (2-[2-{2-(18F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]- quinazoline-6-yl-acrylamide) (18F-PEG6-IPQA) for noninvasive detection of active mutant epidermal growth factor receptor kinase-expressing non-small cell lung cancer xenografts in rodents. In this study, we determined the pharmacokinetics, biodistribution, metabolism, and radiation dosimetry of 18F-PEG6-IPQA in nonhuman primates. Methods: Six rhesus macaques were injected intravenously with 141 ± 59.2 MBq of 18F-PEG6-IPQA, and dynamic PET/CT images covering the thoracoabdominal area were acquired for 30 min, followed by whole-body static images at 60, 90, 120, and 180 min. Blood samples were obtained from each animal at several time points after radiotracer administration. Radiolabeled metabolites in blood and urine were analyzed using high-performance liquid chromatography. The 18F-PEG6-IPQA pharmacokinetic and radiation dosimetry estimates were determined using volume-of-interest analysis of PET/CT image datasets and blood and urine time-activity data. Results: 18F-PEG6-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. 18F-PEG 6 was the major radioactive metabolite. The critical organ was the gallbladder, with an average radiation-absorbed dose of 0.394 mSv/MBq. The other key organs with high radiation doses were the kidneys (0.0830 mSv/MBq), upper large intestine wall (0.0267 mSv/MBq), small intestine (0.0816 mSv/MBq), and liver (0.0429 mSv/MBq). Lung tissue exhibited low uptake of 18F- PEG6-IPQA due to the low affinity of this radiotracer to wild-type epidermal growth factor receptor kinase. The effective dose was 0.0165 mSv/MBq. No evidence of acute cardiotoxicity or of acute or delayed systemic toxicity was observed. On the basis of our estimates, diagnostic dosages of 18F-PEG6-IPQA up to 128 MBq (3.47 mCi) per injection should be safe for administration in the initial cohort of human patients in phase I clinical PET studies. Conclusion: The whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of 18F-PEG6-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.
KW - Epidermal growth factor receptor
KW - F-PEG-IPQA
KW - Nonhuman primate
KW - PET
KW - Radiation dosimetry
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U2 - 10.2967/jnumed.110.086777
DO - 10.2967/jnumed.110.086777
M3 - Article
C2 - 21571803
AN - SCOPUS:79958085032
SN - 0161-5505
VL - 52
SP - 934
EP - 941
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 6
ER -