Radiolabelled somatostatin receptor antagonist versus agonist for peptide receptor radionuclide therapy in patients with metastatic pheochromocytoma or paraganglioma: a retrospective pilot study.

Abstract

Metastatic pheochromocytomas and paragangliomas (mPPGLs) are rare neuroendocrine tumours with limited therapeutic options. Peptide receptor radionuclide therapy (PRRT) using somatostatin receptor (SSTR) antagonists (e.g. [¹⁷⁷Lu]Lu-DOTA-JR11) may achieve higher tumour and organ absorbed doses compared with standard SSTR agonist therapy (e.g. [¹⁷⁷Lu]Lu-DOTA-TOC). This study aimed to perform an intra-patient comparison of tumour and organ dosimetry between [¹⁷⁷Lu]Lu-DOTA-TOC and [¹⁷⁷Lu]Lu-DOTA-JR11 in patients with mPPGLs refractory to conventional therapies. Secondary endpoints included safety and exploratory clinical efficacy of [¹⁷⁷Lu]Lu-DOTA-JR11. In this retrospective pilot study, 6 patients with mPPGLs received 1-2 cycles of [¹⁷⁷Lu]Lu-DOTA-TOC (~ 7.4 GBq/cycle), followed by 1-2 cycles of [¹⁷⁷Lu]Lu-DOTA-JR11 (2 GBq/m² × body surface area) at an interval of 10-12 weeks. Endpoints included estimation of tumour and organ absorbed doses, assessment of safety according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and symptoms, and evaluation of progression-free survival (PFS) before and after [¹⁷⁷Lu]Lu-DOTA-JR11 therapy. Intra-patient comparison showed that the median tumour absorbed dose per cycle was 1.3-fold higher (range 0.9-3.5) with [¹⁷⁷Lu]Lu-DOTA-JR11 than with [¹⁷⁷Lu]Lu-DOTA-TOC. This was associated with longer PFS after [¹⁷⁷Lu]Lu-DOTA-JR11 (12.5 months; range 6 - >20) versus PFS before inclusion (3.5 months; range 1-9). The most severe adverse event was grade 3 lymphopenia in one patient. No thrombocytopenia, neutropenia, creatinine elevation or alanine aminotransferase elevation was observed. [¹⁷⁷Lu]Lu-DOTA-JR11 resulted in higher tumour absorbed doses than [¹⁷⁷Lu]Lu-DOTA-TOC and was associated with longer post-treatment PFS than PFS before inclusion in this small cohort. Treatment was well tolerated, supporting further prospective evaluation in patients with mPPGLs.