Peptide receptor radionuclide therapy in neuroendocrine neoplasms and related tumors: from fundamentals to personalization and the newer experimental approaches

ABSTRACT

Introduction

Peptide Receptor Radionuclide Therapy (PRRT) is a type of molecular-targeted endo-radionuclide therapy in which unsealed radiolabelled somatostatin analogues are specifically directed toward somatostatin receptors (SSTR) over-expressed in Neuroendocrine Neoplasms (NEN) and related malignancies. This modality has witnessed a benchmark growth over last decade and symbolizes remarkable development in precision oncology. The tumor selectivity and excellent tolerability with minimal side effects make this one of the preferred therapeutic options in metastatic progressive NENs.

Areas covered

This review deliberates upon fundamentals of PRRT, its indications and employment as a therapeutic modality for precision oncology. A few special scenarios based on our experiences and expertise have also been mentioned. A short discussion on current advancements worldwide and future directions has also been included.

Expert opinion

SSTR-based PET and PRRT are now an established theranostic approach in management of NENs. Its spectrum has expanded in the form of Neo-Adjuvant-PRRT, Sandwich Chemo-PRRT, Duo-PRRT, Salvage-PRRT, and Intra-arterial-PRRT. Its application to other SSTR-expressing tumors includes metastatic/inoperable medullary thyroid cancer, neural crest malignancies like pheochromocytomas-paragangliomas (PPGLs), Merkel cell carcinoma, radioiodine-refractory thyroid cancer, and meningiomas. Though substantial prospective evidence is still lacking, a multidisciplinary team should adopt PRRT in appropriate indications by using dual tracer PET imaging as a gatekeeper.

KEYWORDS:

• Peptide receptor radionuclide therapy
• PRRT
• somatostatin receptor
• Neuroendocrine tumor (NET)
• PET-CT
• Radionuclides
• ¹⁷⁷Lutetium
• Theranostics

Article highlights

• Peptide Receptor Radionuclide Therapy (PRRT) is a type of endoradionuclide therapy that selectively targets SSTR receptors on various Neuroendocrine and related tumors (e.g. Medullary Thyroid Cancer, Radioiodine non-concentrating or refractory thyroid cancer, Paraganglioma, Pheochromocytomas, Meningiomas, etc.).

• The patients are screened using dual tracer PET/CT, i.e. SSTR-based PET-CT and FDG-PET/CT, and the therapy is suitably administered in advanced, metastatic or inoperable, progressive NETs (traditionally grade 1 and grade 2 showing high uptake in the lesions on SSTR-based imaging).

• PRRT with ¹⁷⁷Lu-DOTATATE has demonstrated efficacy in terms of stabilizing disease and increase in survival rates in multiple studies worldwide and has made its way from bench to bedside. The tumor selectivity of this therapy makes it very well tolerated and safe compared to other systemic options like chemotherapy.

• ¹⁷⁷Lu and ⁹⁰Y are the commonly used therapeutic radioisotopes for the PRRT, while multiple new options including ²²⁵Ac (alpha) radionuclide therapy as well as different types of peptides like SSTR antagonists are currently on the horizon.

• Multiple newer indications, approaches, and combinations with other therapies are being successfully evaluated such as the combination of chemotherapy and PRRT, the combination of two different radionuclides (such as duo – PRRT and tandem PRRT), intra-arterial PRRT, neoadjuvant PRRT, re-challenge/salvage PRRT, etc.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.