Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA0-Tyr3-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors

Noritoshi Kobayashi; Shoko Takano; Kenichi Ito; Madoka Sugiura; Matsuyoshi Ogawa; Yuma Takeda; Naoki Okubo; Akihiro Suzuki; Motohiko Tokuhisa; Tomohiro Kaneta; Daisuke Utsunomiya; Masaharu Hata; Tomio Inoue; Makoto Hosono; Seigo Kinuya; Yasushi Ichikawa

doi:10.1007/s12149-021-01674-9

Safety and efficacy of peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTA⁰-Tyr³-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors

Ann Nucl Med. 2021 Dec;35(12):1332-1341. doi: 10.1007/s12149-021-01674-9. Epub 2021 Sep 17.

Authors

Affiliations

¹ Department of Oncology, Oncology Division, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan. norikoba@yokohama-cu.ac.jp.
² Department of Radiation Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
³ Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁴ Radiation Department, Yokohama City University Hospital, Yokohama, Japan.
⁵ Department of Oncology, Oncology Division, Yokohama City University Graduate School of Medicine, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
⁶ Department of Diagnostic Image Analysis, Graduate School of Medicine, Tohoku University, Sendai, Japan.
⁷ Advanced Medical Center, Shonan Kamakura General Hospital, Kamakura, Japan.
⁸ Department of Radiology, Faculty of Medicine, Kindai University, Higashi-osaka, Japan.
⁹ The Japanese Society of Nuclear Medicine, Tokyo, Japan.

Abstract

Purpose: Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTA⁰-Tyr³-octreotate (¹⁷⁷Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET.

Methods: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of ¹⁷⁷Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs.

Results: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. ¹⁷⁷Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of ¹⁷⁷Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of ¹⁷⁷Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease.

Conclusion: PRRT with ¹⁷⁷Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, ¹⁷⁷Lu-DOTA⁰-Tyr³-octreotate .

Keywords: 177Lu-DOTA0-Tyr3-octreotate; Neuroendocrine tumors; Peptide receptor radionuclide therapy; Phase I; Somatostatin receptor scintigraphy.

MeSH terms

Receptors, Somatostatin*

Substances

Receptors, Somatostatin