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Peer-reviewedCC BY 4.0European Journal of Nuclear Medicine and Molecular Imaging

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

  • Felix Schmidt1
  • Sofia-Maria Lider1,2
  • Lisa McDougall1
  • Christopher Eigler1
  • Peter Bernhardt3
  • Abdulrafee Mushaweh1
  • Andreas Bauman1
  • Melpomeni Fani1
  • Emanuel Christ4,5
  • Damian Wild1,4
5 affiliations
  1. 1Clinic for Radiology and Nuclear Medicine, University Hospital Basel, Petersgraben 4, Basel, CH-4031 Switzerland
  2. 2“Ana Aslan” National Institute of Geriatrics and Gerontology, Bucharest, Romania
  3. 3Department of Medical Radiation Sciences, Institution of Clinical Science, University of Gothenburg, Gothenburg, Sweden
  4. 4ENETS Center of Excellence for Neuroendocrine and Endocrine Tumours, University Hospital Basel, Basel, Switzerland
  5. 5Department of Endocrinology, University Hospital Basel, Basel, Switzerland
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Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: [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.

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Cite

BibTeXRIS
BibTeX
@article{schmidt2026radiolabelled,
  title = {{Radiolabelled somatostatin receptor antagonist versus agonist for peptide receptor radionuclide therapy in patients with metastatic pheochromocytoma or paraganglioma: a retrospective pilot study}},
  author = {Felix Schmidt and Sofia-Maria Lider and Lisa McDougall and Christopher Eigler and Peter Bernhardt and Abdulrafee Mushaweh and Andreas Bauman and Melpomeni Fani and Emanuel Christ and Damian Wild},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = aug,
  doi = {10.1007/s00259-026-08122-8},
  url = {https://doi.org/10.1007/s00259-026-08122-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Radiolabelled somatostatin receptor antagonist versus agonist for peptide receptor radionuclide therapy in patients with metastatic pheochromocytoma or paraganglioma: a retrospective pilot study
AU  - Felix Schmidt
AU  - Sofia-Maria Lider
AU  - Lisa McDougall
AU  - Christopher Eigler
AU  - Peter Bernhardt
AU  - Abdulrafee Mushaweh
AU  - Andreas Bauman
AU  - Melpomeni Fani
AU  - Emanuel Christ
AU  - Damian Wild
PY  - 2026
DA  - 2026/08/12
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08122-8
UR  - https://doi.org/10.1007/s00259-026-08122-8
AB  - Purpose: 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.  Methods: 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.  Results: 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.  Conclusion: [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.
SN  - 1619-7070
SN  - 1619-7089
ER  -