Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides—Where Are We Now

SIMPLE SUMMARY: Neuroendocrine neoplasms (NENs) are a rare and diverse group of malignancies which are rising in incidence. Several treatments have been devised for unresectable or metastatic tumors, including peptide receptor radionuclide therapy (PRRT). PRRT specifically targets cells that express high levels of somatostatin receptors, such as well-or moderately differentiated NENs, to enable precise delivery. This article highlights the journey of PRRT from inception to the present day, where it is now integral in clinical practice guidelines worldwide. It also provides an overview of NENs and a history of somatostatin receptor imaging, which facilitates the selection of patients for PRRT. Practical considerations relating to appropriate use, treatment administration and side-effects are discussed, and perspectives on future directions to boost efficacy are detailed. ABSTRACT: Peptide receptor radionuclide therapy (PRRT) has been one of the most successful and exciting examples of theranostics in nuclear medicine in recent decades and is now firmly embedded in many treatment algorithms for unresectable or metastatic neuroendocrine neoplasms (NENs) worldwide. It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of somatostatin receptors that can be selectively targeted. This review article outlines the scientific basis of PRRT in treatment of NENs and describes its discovery dating back to the early 1990s. Early treatments utilizing Indium-111, a γ-emitter, showed promise in reduction in tumor size and improvement in biochemistry, but were also met with high radiation doses and myelotoxic and nephrotoxic effects. Subsequently, stable conjugation of DOTA-peptides with β-emitting radionuclides, such as Yttrium-90 and Lutetium-177, served as a breakthrough for PRRT and studies highlighted their potential in eliciting progression-free survival and quality of life benefits. This article will also elaborate on the key trials which paved the way for its approval and will discuss therapeutic considerations, such as patient selection and administration technique, to optimize its use.