90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans

Abstract

The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177. In this review, covering twenty five years of literature, we describe the characteristics and performances of the two most used therapeutic radiopharmaceuticals for the NETs radio-treatment: [⁹⁰Y]Y-DOTATOC and [¹⁷⁷Lu]Lu-DOTATOC taking this opportunity to retrace the most significant results that have determined their success, promoting them from preclinical studies to application in humans.

Keywords: PRRT; [177Lu]Lu-DOTATOC; [90Y]Y-DOTATOC; neuroendocrine tumors.

Figure 1

Schematic representation of peptide receptor radionuclide with radiolabeled somatostatin analogues (PRRT) therapeutic model. This is based on the existence of a target, overexpressing SST-Rs and a radiopharmaceutical, consisting of peptide which have a high affinity for the SST-Rs expressed by the target, an adequate radioactive isotope and a chelator able to stable bond the radionuclide.

Figure 2

Chemical structure of [⁹⁰Y]Y-DOTATOC and [¹⁷⁷Lu]Lu-DOTATOC = ⁹⁰Y or ¹⁷⁷Lu.

Figure 3

Decay schemes of ⁹⁰Y (a) and ¹⁷⁷Lu (b).

Figure 4

[¹⁷⁷Lu]Lu-DOTA-TOC and [⁹⁰Y]Y-DOTATOC synthesis (a), dilution and sterilization (b) and manual fractionation (c).