Evaluation of receptors for somatostatin in various tumors using different analogs

Published on Thursday, 22 February 2018


The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues.

In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature.

Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites.

Superactive octapeptide analogs of somatostatin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors.

Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers.

Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2 (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14.

Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers.

In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I.

Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggest that differences may exist between somatostatin receptors not only in normal vs. cancerous tissues, but also among various tumors.

Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors.


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See also:

- Somatostatin in oncology, the overlooked evidences;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, LAR analogues and/or derivatives);

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- Neuroblastoma: Complete objective response to biological treatment.