Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

Abstract

Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.

Synthesis of Poly(Malic Acid) Derivatives End-Functionalized with Peptides and Preparation of Biocompatible Nanoparticles to Target Hepatoma Cells

“…Beside their uses as therapeutic molecules [ 18 , 22 , 23 , 25 ], short peptides have been quite recently developed as targeting agents, since it was shown that peptide receptors are overexpressed, or even exclusively expressed, in tumors [ 12 ]. Such increasing interest has been catalyzed by the discovery, at the end of the 1980s, of specific receptors to somatostatin (SSTR1-5) expressed by human neuroendocrine tumors (NETs) and their metastases [ 12 , 26 ]. Octreotide, a somatostatin analog, grafted to diethylenetriamine pentaacetic acid (DTPA) chelating indium 111 ( 111 In) was approved by the US Food and Drug Administration (FDA) in 1994 under the name of OctreoScan ® for the diagnosis and localization of NETs overexpressing the somatostatin receptor SSTR2 [ 12 , 27 ].…”

Medical Imaging in the Diagnosis of Schistosomiasis: A Review

“…Beyond 18 F-FDG, other PET tracers are commonly used in the evaluation of infections and inflammations: an example is represented by radiolabeled somatostatin analogues, radiopharmaceuticals that bind somatostatin receptors with high affinity [ 86 , 87 , 88 ]. Theoretically, we may suppose the applicability of these PET tracers in the assessment of inflammatory status induced by schistosome infection (it is well-demonstrated that somatostatin receptors are expressed by inflammatory cells) [ 89 ].…”

A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy

“… 162 , 163 , 164 , 165 , 166 , 167 , 168 Most recent research using HSV1-tk is directed toward cell therapies. 169 , 170 , 171 , 172 , 173 The use of deep-tissue imaging modalities for large animals is also much more translatable to human trials than OI, increasing the value of large animal imaging for pre-clinical validation. Further development of RGI methods for large animals will facilitate efficient translation of novel therapeutics.…”