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Biodistribution and radiation dosimetry of the novel hypoxia PET probe [F-18]DiFA and comparison with [F-18]FMISO

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Title: Biodistribution and radiation dosimetry of the novel hypoxia PET probe [F-18]DiFA and comparison with [F-18]FMISO
Authors: Watanabe, Shiro Browse this author →KAKEN DB
Shiga, Tohru Browse this author →KAKEN DB
Hirata, Kenji Browse this author →KAKEN DB
Magota, Keiichi Browse this author →KAKEN DB
Okamoto, Shozo Browse this author →KAKEN DB
Toyonaga, Takuya Browse this author
Higashikawa, Kei Browse this author →KAKEN DB
Yasui, Hironobu Browse this author →KAKEN DB
Kobayashi, Jun Browse this author
Nishijima, Ken-ichi Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Matsumoto, Hiroki Browse this author
Kuge, Yuji Browse this author →KAKEN DB
Tamaki, Nagara Browse this author →KAKEN DB
Keywords: Hypoxia
New tracer
Issue Date: 5-Jul-2019
Publisher: Springer (SpringerOpen)
Journal Title: EJNMMI research
Volume: 9
Start Page: 60
Publisher DOI: 10.1186/s13550-019-0525-6
PMID: 31278504
Abstract: BackgroundTo facilitate hypoxia imaging in a clinical setting, we developed 1-(2,2-dihydroxymethyl-3-[F-18]-fluoropropyl)-2-nitroimidazole ([F-18]DiFA) as a new tracer that targets tumor hypoxia with its lower lipophilicity and efficient radiosynthesis. Here, we evaluated the radiation dosage, biodistribution, human safety, tolerability, and early elimination after the injection of [F-18]DiFA in healthy subjects, and we performed a preliminary clinical study of patients with malignant tumors in a comparison with [F-18]fluoromisonidazole ([F-18]FMISO).ResultsThe single administration of [F-18]DiFA in 8 healthy male adults caused neither adverse events nor abnormal clinical findings. Dynamic and sequential whole-body scans showed that [F-18]DiFA was rapidly cleared from all of the organs via the hepatobiliary and urinary systems. The whole-body mean effective dose of [F-18]DiFA estimated by using the medical internal radiation dose (MIRD) schema with organ level internal dose assessment/exponential modeling (OLINDA/EXM) computer software 1.1 was 14.40.7 mu Sv/MBq. Among the organs, the urinary bladder received the largest absorbed dose (94.7 +/- 13.6 mu Sv/MBq). The mean absorbed doses of the other organs were equal to or less than those from other hypoxia tracers. The excretion of radioactivity via the urinary system was very rapid, reaching 86.4 +/- 7.1% of the administered dose. For the preliminary clinical study, seven patients were subjected to [F-18]FMISO and [F-18]DiFA positron emission tomography (PET) at 48-h intervals to compare the two tracers' diagnostic ability for tumor hypoxia. The results of the tumor hypoxia evaluation by [F-18]DiFA PET at 1h and 2h were not significantly different from those obtained with [F-18]FMISO PET at 4h ([F-18]DiFA at 1h, p=0.32; [F-18]DiFA at 2h, p=0.08). Moreover, [F-18]DiFA PET at both 1h (k=0.68) and 2h (k=1.00) showed better inter-observer reproducibility than [F-18]FMISO PET at 4h (k=0.59).Conclusion [F-18]DiFA is well tolerated, and its radiation dose is comparable to those of other hypoxia tracers. [F-18]DiFA is very rapidly cleared via the urinary system. [F-18]DiFA PET generated comparable images to [F-18]FMISO PET in hypoxia imaging with shorter waiting time, demonstrating the promising potential of [F-18]DiFA PET for hypoxia imaging and for a multicenter trial.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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