Somatostatin Receptor Based Imaging and Radionuclide Therapy

Abstract

Somatostatin (SST) receptors (SSTRs) belong to the typical 7-transmembrane domain family of G-protein-coupled receptors. Five distinct subtypes (termed SSTR1-5) have been identified, with SSTR2 showing the highest affinity for natural SST and synthetic SST analogs. Most neuroendocrine tumors (NETs) have high expression levels of SSTRs, which opens the possibility for tumor imaging and therapy with radiolabeled SST analogs. A number of tracers have been developed for the diagnosis, staging, and treatment of NETs with impressive results, which facilitates the applications of human SSTR subtype 2 (hSSTr2) reporter gene based imaging and therapy in SSTR negative or weakly positive tumors to provide a novel approach for the management of tumors. The hSSTr2 gene can act as not only a reporter gene for in vivo imaging, but also a therapeutic gene for local radionuclide therapy. Even a second therapeutic gene can be transfected into the same tumor cells together with hSSTr2 reporter gene to obtain a synergistic therapeutic effect. However, additional preclinical and especially translational and clinical researches are needed to confirm the value of hSSTr2 reporter gene based imaging and therapy in tumors.

Somatostatin Receptor Expression Is Associated With Metastasis and Patient Outcome in Pulmonary Carcinoid Tumors

“…Neuroendocrine tumors (NETs) overexpress SSTRs, which provides a molecular basis for tumor imaging and therapeutic interventions with somatostatin analogs (SSAs) (9,10). Firstgeneration SSAs, octreotide and lanreotide, are approved for carcinoid symptom control as well as for antitumor activity in metastatic NETs (11).…”

Development of a radiolabeled caninized anti-EGFR antibody for comparative oncology trials

“…The most commonly applied is the SSTR-ligand [ 111 In-DTPA 0 ]octreotide, which is used for diagnosis and staging. Tumors being positively marked by [ 111 In-DTPA 0 ]octreotide can be treated subsequently with SSTR-ligand bound therapeutic radionuclides, such as [ 90 Y-DOTA0-Tyr 3 ]octreotide ( 90 Y-DOTATOC) and [ 177 Lu-DOTA0-Tyr 3 ]octreotate [ 20 – 22 ]. Such combinations of diagnostically- and therapeutically-labeled molecules are often called “theranostic twins” [ 23 ].…”

Gastrointestinal Neuroendocrine Tumors: Clinical and Pathological Correlates

“…It has been suggested that yttrium may be more effective for larger masses, whereas lutetium may be better suited for smaller lesions. 51 Lutetium-177-DOTA-octreotate is the only compound to have been tested in a phase 3 trial. In this study, the agent was associated with a significant improvement in progression-free survival (p < 0.001), but only a modest fraction of patients demonstrated objective tumor response.…”