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

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Abstract

Objective

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

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Acknowledgments

We thank Dr. Yasushi Takagi of Showa University and Dr. Ukihide Tateishi of Tokyo Medical and Dental University for their support in the study design and data interpretation. We also thank the subjects as well as the staff of the Biomedical Research Center and the Department of Radiology at Kitasato University Kitasato Institute Hospital for their participation in the study.

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Authors and Affiliations

  1. Biomedical Research Center, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan

    Yoshinori Yamada & Hiroshi Nakatani

  2. Department of Diagnostic Radiology and Interventional Radiology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan

    Hisashi Yanaihara

  3. Clinical Development Department, Nihon Medi-Physics Co., Ltd., Tokyo, Japan

    Masahiro Omote

Authors
  1. Yoshinori Yamada
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  2. Hiroshi Nakatani
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  3. Hisashi Yanaihara
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  4. Masahiro Omote
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Correspondence to Yoshinori Yamada.

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Conflict of interest

This study was sponsored by Nihon Medi-Physics Co., Ltd (Tokyo, Japan). Pharma International Co., Ltd (Tokyo, Japan) supported the preparation of the article and the cost of the preparation was borne by Nihon Medi-Physics. Masahiro Omote is an employee of Nihon Medi-Physics.

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Yamada, Y., Nakatani, H., Yanaihara, H. et al. Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults. Ann Nucl Med 29, 792–798 (2015). https://doi.org/10.1007/s12149-015-1006-2

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  • DOI: https://doi.org/10.1007/s12149-015-1006-2

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