Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults

Objective Technetium etarfolatide ( 99m Tc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors. Administering folic acid prior to the administration of 99m Tc-EF has been shown to improve SPECT images. Here, we conducted a phase I clinical trial to assess the safety, pharmacokinetics, and radiation dosimetry of 99m Tc-EF injection following pre-administration of folic acid in healthy Japanese male adults. Methods Six healthy Japanese male adults were enrolled in the study. Folic acid was intravenously administered, followed 1–3 min later by an intravenous injection of 99m Tc-EF (740 MBq ± 20 %). Assessments of subjective symptoms and objective findings, electrocardiograms, physical examination, and laboratory tests were performed before and up to 7 days after the injection to assess the safety of 99m Tc-EF. Blood and urine collections and whole-body planar imaging were conducted at various time points up to 24 h after the injection to assess the pharmacokinetics of 99m Tc-EF. The internal radiation dosimetry was calculated based on the pharmacokinetics results using the MIRD method. Results Five adverse events were observed in three subjects (50 %) after administration of the folic acid and 99m Tc-EF, while these events were mild and non-serious. Of those five events, three were considered to be related to the administered agents. The radioactivity in blood rapidly decreased and showed a biphasic profile. The activity of 99m Tc-EF at 5 min post injection was largest in the bone marrow, followed by the liver and kidneys, and had decreased within 24 h in all organs/tissues without appreciable retention. The pharmacokinetics results suggested that 99m Tc-EF was mainly eliminated by kidney. The results also suggested that when administered at 925 MBq of 99m Tc-EF, which is the maximum dose generally used for clinical trials in other countries, the corresponding effective dose of 99m Tc-EF is equal to or less than those determined for the current radioactive diagnostic imaging agents. Conclusions The results of this study assessing the safety and radiation dosimetry of 99m Tc-EF with folic acid pre-administration suggested that folic acid and 99m Tc-EF should be appropriate for further studies. No pharmacokinetics concerns were noted.