Strategies Towards Improving Clinical Outcomes of Peptide Receptor Radionuclide Therapy

Abstract

Purpose of review: Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu-DOTA⁰,Tyr³] octreotate is an effective and safe second- or third-line treatment option for patients with low-grade advanced gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). In this review, we will focus on possible extensions of the current use of PRRT and on new approaches which could further improve its treatment efficacy and safety.

Recent findings: Promising results were published regarding PRRT in other NENs, including lung NENs or high-grade NENs, and applying PRRT as neoadjuvant or salvage therapy. Furthermore, a diversity of strategic approaches, including dosimetry, somatostatin receptor antagonists, somatostatin receptor upregulation, radiosensitization, different radionuclides, albumin binding, alternative renal protection, and liver-directed therapy in combination with PRRT, have the potential to improve the outcome of PRRT. Also, novel biomarkers are presented that could predict response to PRRT. Multiple preclinical and early clinical studies have shown encouraging potential to advance the clinical outcome of PRRT in NEN patients. However, at this moment, most of these strategies have not yet reached the clinical setting of randomized phase III trials.

Keywords: Neuroendocrine tumour; Peptide receptor radionuclide therapy.

Fig. 1

Overview of future possibilities that could extent the use of PRRT or could improve the efficacy and safety of PRRT. NEN neuroendocrine neoplasm, SSTR somatostatin receptor, Hsp90 heat shock protein 90, PARP poly(ADP-ribose) polymerase