Combination treatments to enhance peptide receptor radionuclide therapy of neuroendocrine tumours. 2020

Samuel Adant, and Girish M Shah, and Jean-Mathieu Beauregard
Department of Radiology and Nuclear Medicine and Cancer Research Centre, Université Laval, Quebec City, QC, Canada.

The incidence of neuroendocrine tumours (NETs) is increasing, but curative therapeutic options are limited because diagnosis is often delayed until the tumour has metastasized. Peptide receptor radionuclide therapy (PRRT) is among the most effective therapeutic options for metastatic NETs because of targeted delivery of radioactivity to the tumour via the somatostatin receptor (SSTR) and relatively low systemic toxicity. However, current PRRT regimes result in palliation rather than cure, and higher doses of PRRT that might achieve remission would also be too toxic to the patients. Therefore, there is a need to improve PRRT of NETs by combining it with other agents to achieve maximum benefits from the internal radiation therapy, while sparing non-target organs from radiation toxicity. Here we review various current and potential combination strategies to improve 177Lu-octreotate-based PRRT of NET, some of which could also apply to other radionuclide therapies. These strategies include co-administered drugs that improve delivery of the radiopharmaceutical via increased tumour perfusion or through increased SSTR density at tumour surface. Other combinations are aimed at enhancing the biological effects of the radiation-induced DNA damage in tumour cells or generating additional DNA damage burden to effectively increase the cytotoxicity of PRRT. We also propose an algorithm for stratifying NET patients to receive or not combination therapies with PRRT. Considering that PRRT and many of these combination agents are already used for treating patients with NET and other cancers, the proposed strategies to improve the efficacy of PRRT could be rapidly translated into the clinic.

UI MeSH Term Description Entries
D011868 Radioisotopes Isotopes that exhibit radioactivity and undergo radioactive decay. (From Grant & Hackh's Chemical Dictionary, 5th ed & McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Daughter Isotope,Daughter Nuclide,Radioactive Isotope,Radioactive Isotopes,Radiogenic Isotope,Radioisotope,Radionuclide,Radionuclides,Daughter Nuclides,Daugter Isotopes,Radiogenic Isotopes,Isotope, Daughter,Isotope, Radioactive,Isotope, Radiogenic,Isotopes, Daugter,Isotopes, Radioactive,Isotopes, Radiogenic,Nuclide, Daughter,Nuclides, Daughter
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015282 Octreotide A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula. Octreotide Acetate,Compound 201-995,Octreotide Acetate Salt,SAN 201-995,SM 201-995,SMS 201-995,Sandostatin,Sandostatine,Sandoz 201-995,Compound 201 995,Compound 201995,SAN 201 995,SAN 201995,SM 201 995,SM 201995,SMS 201 995,SMS 201995,Sandoz 201 995,Sandoz 201995
D018000 Receptors, Peptide Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells. Peptide Hormone Receptors,Peptide Receptors,Peptide Hormone Receptor,Peptide Receptor,Receptors, Peptide Hormones,Receptors, Peptides,Hormone Receptor, Peptide,Hormone Receptors, Peptide,Hormones Receptors, Peptide,Peptide Hormones Receptors,Peptides Receptors,Receptor, Peptide,Receptor, Peptide Hormone,Receptors, Peptide Hormone
D018358 Neuroendocrine Tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition. Neuroendocrine Tumor,Tumor, Neuroendocrine,Tumors, Neuroendocrine
D019275 Radiopharmaceuticals Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161) Radiopharmaceutical

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