What does this research mean for the field?

Peptide receptor radionuclide therapy with XTR008 (177Lu-DOTATATE) demonstrates favorable pharmacokinetics, dosimetry, and tolerability in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study investigates the pharmacokinetic and dosimetry profile of XTR008 in patients with advanced gastroenteropancreatic neuroendocrine tumors.

June 7, 2026

Pharmacokinetics and Dosimetry of 177 Lu-DOTATATE in Patients with Advanced Well-Differentiated, Gastroenteropancreatic Neuroendocrine Tumors: Results from a Substudy of the Phase 3 XT-XTR008-3-01 Trial

Key Points

This study investigates the pharmacokinetic and dosimetry profile of XTR008 in patients with advanced gastroenteropancreatic neuroendocrine tumors.
10 patients received 4 cycles of 177Lu-DOTATATE (7.4 GBq/cycle) during the trial XT-XTR008-3-01.
Post-first dose assessments included whole-body scintigraphy, abdominal SPECT/CT, and blood and urine sampling for PK, safety, and efficacy.
Etiological data from organ doses and toxicity were analyzed, recording hematological toxicities and objective response rates.
177Lu-DOTATATE peaked in blood at 15 min, with a half-life of 37.36 ± 16.44 h, and 60.38% excreted in urine within 16 h.
Mean absorbed doses to kidneys and red marrow were 18.914 ± 6.242 Gy and 1.199 ± 0.337 Gy, respectively, with some patients exceeding 23 Gy without renal toxicity.
The objective response rate was 30% (3/10), with no significant difference in tumor dose between responders and nonresponders (p = 0.44).

Abstract

This substudy presents the exploratory pharmacokinetic (PK) and dosimetry profile of XTR008, 177Lu-DOTATATE developed in China, from the phase 3 trial XT-XTR008-3-01. 10 patients with well-differentiated, locally advanced, or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) received 4 cycles of 177Lu-DOTATATE (7.4 GBq/cycle). Postfirst dose, whole-body planar scintigraphy (up to 7 days), abdominal SPECT/CT (24/48 h), and blood and urine sampling for PK, safety, and efficacy assessment were performed. 177Lu-DOTATATE peaked in blood at 15 min, then decreased with a T1/2 of 37.36 ± 16.44 h. 60.38% was excreted in urine within 16 h. For four cycles, the mean absorbed doses to kidneys and red marrow were 18.914 ± 6.242 Gy (excluding one patient with nephrolithiasis and absorbed dose to kidneys of 77.1Gy) and 1.199 ± 0.337 Gy, respectively. Two patients had absorbed doses to the kidneys higher than 23 Gy (25.9 Gy, 23.1 Gy) without renal toxicity. Hematological toxicities (mostly grade 1/2) were the most common treatment-related adverse events (TRAEs). No significant association was found between organ doses and specific toxicities. Tumor absorbed dose varied widely (0.312–9.78 Gy/GBq). An objective response rate (ORR) was 30% (3/10); tumor dose did not significantly differ between responders (2.68 ± 2.53 Gy/GBq) and nonresponders (2.93 ± 1.81 Gy/GBq, p = 0.44). Tumor dose correlated moderately but nonsignificantly with size change (r = 0.016, p > 0.05). PRRT with XTR008 showed favorable tolerability, PK, and dosimetry in patients with advanced GEP-NETs, supporting its use in Chinese patients with well-differentiated GEP-NETs as a new treatment option.

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