Phase I clinical trial of ^sup 99m^Tc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults

Objective Technetium etarfolatide (^sup 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 ^sup 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 ^sup 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 ^sup 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 ^sup 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 ^sup 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 ^sup 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 ^sup 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 ^sup 99m^Tc-EF was mainly eliminated by kidney. The results also suggested that when administered at 925 MBq of ^sup 99m^Tc-EF, which is the maximum dose generally used for clinical trials in other countries, the corresponding effective dose of ^sup 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 ^sup 99m^Tc-EF with folic acid pre-administration suggested that folic acid and ^sup 99m^Tc-EF should be appropriate for further studies. No pharmacokinetics concerns were noted.