The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours

Abstract

Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with high affinity and specificity receptors overexpressed on tumours. PRRNT employing the radiotagged somatostatin receptor agonists 90Y-DOTATOC ([90Y-DOTA0,Tyr3]-octreotide) or 177Lu-DOTATATE ([177Lu-DOTA0,Tyr3,Thr8]-octreotide or [177Lu-DOTA0,Tyr3]-octreotate) have been successfully used for the past 15 years to target metastatic or inoperable neuroendocrine tumours expressing the somatostatin receptor subtype 2. Accumulated evidence from clinical experience indicates that these tumours can be subjected to a high absorbed dose which leads to partial or complete objective responses in up to 30 % of treated patients. Survival analyses indicate that patients presenting with high tumour receptor expression at study entry and receiving 177Lu-DOTATATE or 90Y-DOTATOC treatment show significantly higher objective responses, leading to longer survival and improved quality of life. Side effects of PRRNT are typically seen in the kidneys and bone marrow. These, however, are usually mild provided adequate protective measures are undertaken. Despite the large body of evidence regarding efficacy and clinical safety, PRRNT is still considered an investigational treatment and its implementation must comply with national legislation, and ethical guidelines concerning human therapeutic investigations. This guidance was formulated based on recent literature and leading experts’ opinions. It covers the rationale, indications and contraindications for PRRNT, assessment of treatment response and patient follow-up. This document is aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRNT and to deliver the treatment in a safe and effective manner. This document is largely based on the book published through a joint international effort under the auspices of the Nuclear Medicine Section of the International Atomic Energy Agency.

Neuroendocrine Neoplasms: A Case Report with Complete Reverse Mismatch and the Correlation with Differentiation Rate

“…The present and future trend in oncological care heads towards personalizing treatments in order to reduce the side effects of current available therapies and individualizing management to each patient. And this is where the Nuclear Medicine Therapeutics is a cornerstone in achieving the objective [6][7][8][9][10][11][12][13][14][15][16][17].…”

Therapeutic radionuclides in nuclear medicine: current and future prospects

“…Due to various peptide receptors being overexpressed on tumour cells, peptide receptor radionuclide therapy has been a promising therapeutic strategy that makes use of high tumour receptor expression to deliver radiation selectively to targeted tumours while sparring the normal tissues (Zaknun et al, 2013). Since radiolabelled peptides display unique characteristics, such as rapid whole-body clearance and tissue penetration, low antigenicity, and convenient production, a series of radiolabelled peptides has been designed for diagnostic and therapeutic applications in oncology (Teunissen et al, 2005;Valkema et al, 2006;Bartolomei et al, 2009;Bodei et al, 2009;Maecke and Reubi, 2011).…”

Compartment Biokinetic Model for 90y-Dotatoc

“…90 Y-DOTATOC ([Y-DOTA0, Tyr3] -octreotide) has been successfully utilized during in the past 15 years for the treatment of neuroendocrine tumors that are inoperable, or metastatic, which express the somatostatin receptor type 2 [2,3]. 90 Y is a pure β-emitter, whose physical half-life is 64 h. The energy of the released β-particles is up to 2.28 MeV, range of beta particles in soft tissues is short, consequently killing the cells near the point of emission.…”