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Molecular imaging and radioligand therapies in pheochromocytomas and paragangliomas

Jorge H Hernandez-Felix1,2, Mahshid Golagha1, Abhishek Jha3

  • 1Developmental Therapeutics Clinic, National Cancer Institute (NCI), National Institutes of Health , Bethesda, Maryland, USA.

Endocrine-Related Cancer
|July 15, 2026
PubMed

Insights

Pheochromocytomas and paragangliomas (PPGLs) are rare tumors. Advances in genetic testing and functional imaging, including radioligand therapies, offer new management strategies for advanced or metastatic PPGLs.

Area of Science:

  • Endocrinology
  • Oncology
  • Nuclear Medicine

Background:

  • Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with significant heterogeneity.
  • Surgical resection is curative, but many patients present with unresectable, metastatic, or progressive disease requiring alternative treatments.
  • Genetic advances identify germline variants in 30-40% of cases, aiding classification and targeted therapies.

Purpose of the Study:

  • To review current and emerging diagnostic and therapeutic strategies for pheochromocytomas and paragangliomas (PPGLs).
  • To highlight the role of molecularly targeted imaging and radioligand therapies in managing advanced PPGLs.
  • To discuss the impact of genetic findings on PPGL classification and treatment selection.

Main Methods:

  • Review of functional imaging modalities (e.g., DOTA-SSA, FDOPA, FDG, MIBG) exploiting tumor biology.
  • Analysis of radioligand therapies, including 131I-MIBG and 177Lu-DOTATATE (Peptide Receptor Radionuclide Therapy - PRRT).
  • Discussion of ongoing research into genetically defined subgroups and combination therapies.

Main Results:

  • Functional imaging improves diagnostic accuracy, prognosis, and therapy selection for PPGLs.
  • High-specific-activity 131I-MIBG shows durable disease control and symptomatic improvement in metastatic PPGLs.
  • Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE demonstrates high disease control rates (80-100%).

Conclusions:

  • Molecularly targeted imaging and radioligand therapies are pivotal in managing advanced pheochromocytomas and paragangliomas (PPGLs).
  • 131I-MIBG and 177Lu-DOTATATE offer effective treatment options with favorable safety profiles.
  • Future research focuses on personalized PRRT strategies and radiosensitizing combinations for improved patient outcomes.
Keywords:
123I-MIBG131I-MIBG177Lu-DOTATATE18F-FDG18F-FDOPA68Ga-DOTATATEPRRTparagangliomapheochromocytomaradionuclide therapy

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