Next-Generation Peptide Receptor Radionuclide Therapy: A Phase 1 Dose-Escalation and Dosimetry Study of ¹⁷⁷Lu-DOTA-EB-TATE.

Authors

Lisa Bodei, Pat Zanzonico, Simone Krebs, Diane Reidy-Lagunes, Nitya Raj, Serge K Lyashchenko, Jason S Lewis, Heiko Schöder, Joseph A O'Donoghue

Published in

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. Sep 24, 2026. Epub Sep 24, 2026.

Abstract

Neuroendocrine tumors (NETs) are often detected late, limiting curative treatments and requiring systemic therapies such as peptide receptor radionuclide therapy (PRRT). Although ¹⁷⁷Lu-DOTATATE has demonstrated efficacy, its rapid clearance from the circulation limits tumor radiation delivery and may increase renal toxicity risk. ¹⁷⁷Lu-DOTA-EB-TATE, a novel PRRT agent conjugated with Evans blue for albumin binding, offers extended circulation time and enhanced tumor uptake, potentially improving therapeutic outcomes. This phase 1 study aimed to evaluate the safety, dosimetry, and preliminary efficacy of ¹⁷⁷Lu-DOTA-EB-TATE in patients with advanced gastroenteropancreatic NETs. Methods: Six adults with inoperable, measurable gastroenteropancreatic NETs (WHO grades 2 and 3) and with somatostatin receptor overexpression were enrolled. Using a 3 + 3 dose-escalation design, patients received ¹⁷⁷Lu-DOTA-EB-TATE at nominal activities of 1.85, 3.70, or 5.55 GBq intravenously for 2 cycles, 6 wk apart. Individualized dosimetry after the first cycle informed subsequent treatment delivery. Safety was assessed biweekly, and tumor responses were evaluated using RECIST at 3 and 6 mo. Results: Treatment was well-tolerated, with mild side effects, including nausea, fatigue, and hair loss; no renal toxicity occurred. The median kidney absorbed dose per cycle was 4.8 Gy (range, 2.9-8.9 Gy; mean, 2.2 Gy/GBq). Hematologic toxicity was dose-limiting, with persistent grade 3 febrile neutropenia observed at 3.7 GBq in 1 patient and confirmed in an external cohort. Thus, the maximum tolerated activity was set at 3.70 GBq and the recommended phase 2 activity at 1.85 GBq per cycle to avoid irreversible marrow suppression. Tumor responses included stable disease (n = 5) and partial response (n = 1) at 3 mo; disease progressed in 2 patients at 6 mo after treatment completion. Conclusion: The 2-cycle regimen of ¹⁷⁷Lu-DOTA-EB-TATE delivered higher renal absorbed doses compared with standard ¹⁷⁷Lu-DOTATATE. With individualized dosimetry, no kidney toxicity was observed. However, increased retention in the circulation caused hematologic-related side effects and made marrow the dose-limiting organ. Within the defined dosing limits of this study, ¹⁷⁷Lu-DOTA-EB-TATE is a potential high-uptake alternative to standard PRRT, supporting a shortened 2-cycle schedule for earlier response assessment. Further research should refine dosing schedules and patient selection to balance efficacy and safety.

PMID:
42785949
Bibliographic data and abstract were imported from PubMed on 25 Sep 2026.

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