ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2011
Whole-body biodistribution kinetics, metabolism, and radiation dosimetry estimates of 18F-PEG6-IPQA in nonhuman primates.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 15 citations in OpenAlex.
- A new pharmacokinetic model forScientific reports · 2018Trial
- MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Imaging Intratumoral Nanoparticle Uptake After Combining Nanoembolization with Various Ablative Therapies in Hepatic VX2 Rabbit Tumors.Journal of biomedical nanotechnology · 2016Article
- Radiopharmaceuticals as probes to characterize tumour tissue.European journal of nuclear medicine and molecular imaging · 2015Review
- Hybrid microPET imaging for dosimetric applications in mice: improvement of activity quantification in dynamic microPET imaging for accelerated dosimetry applied to 6-[18 F]fluoro-L-DOPA and 2-[18 F]fluoro-L-tyrosine.Molecular imaging and biology · 2014Article
- Tumor uptake of hollow gold nanospheres after intravenous and intra-arterial injection: PET/CT study in a rabbit VX2 liver cancer model.Molecular imaging and biology · 2013Article
- Imaging epigenetic regulation by histone deacetylases in the brain using PET/MRI with ¹⁸F-FAHA.NeuroImage · 2013Article
- Positron emission tomography (PET) imaging with (18)F-based radiotracers.American journal of nuclear medicine and molecular imaging · 2012Article
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14 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledWe recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2-(2-[2-{2-((18)F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide) ((18)F-PEG(6)-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 (18)F-PEG(6)-IPQA in nonhuman primates.
methodsSix rhesus macaques were injected intravenously with 141 ± 59.2 MBq of (18)F-PEG(6)-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 (18)F-PEG(6)-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(18)F-PEG(6)-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. (18)F-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 (18)F-PEG(6)-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 (18)F-PEG(6)-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.
conclusionThe whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of (18)F-PEG(6)-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.
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