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Review
. 2017 Jan 27:10:551-557.
doi: 10.2147/OTT.S97584. eCollection 2017.

Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

Stefano Severi  1 , Ilaria Grassi  1 , Silvia Nicolini  1 , Maddalena Sansovini  1 , Alberto Bongiovanni  2 , Giovanni Paganelli  1
Affiliations
Review

Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

Stefano Severi et al. Onco Targets Ther. .

Abstract

Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%-70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided.

Keywords: 177Lu-Dotatate; 90Y-Dotatoc; delivered activity; neuroendocrine malignancies; radiolabelled receptors; radiopharmaceutical.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Patient with progressive GEP-NET treated at our institute. Notes: Total body images acquired after the first (A) and fifth (B) cycle of 90Y-Dotatoc. Cumulative activity delivered was 8.14 GBq. Abbreviations: GEP, gastroenteropancreatic; NET, neuroendocrine tumor; 90Y-Dotatoc, 90Y-DOTA-Tyr3-octreotide.
Figure 2
Figure 2
(A) PFS curves of the same group of patients after treatment with 90Y-Dotatoc and after retreatment with low-dose 177Lu-Dotatate. (B) OS curve for retreatment group. Note: It was not possible to elaborate a posttreatment OS curve as all of the patients included in the study were originally treated in different centers in Italy. Abbreviations: PFS, progression-free survival; OS, overall survival; 90Y-Dotatoc, 90Y-DOTA-Tyr3-octreotide; 177Lu-Dotatate, 177Lu-DOTA-Tyr3-octreotate.
See this image and copyright information in PMC

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