Molecular radiotherapy with somatostatin analogs for (neuro-)endocrine tumors.

Peptide receptor radionuclide therapy (PRRT) holds great promise for the future regarding the treatment of various cancers. With the use of radiolabelled peptides, which bind with high affinity to their receptors on cancer cells, it is possible to target the cancer efficiently. In gastroenteropancreatic tumors, radiolabelled somatostatin analog therapy has proven to be effective. Dose-limiting organs are the bone marrow and the kidneys. With the currently used dose schemes and kidney protection, PRRT is relatively safe and serious side-effecs are rare. Which radiolabelled somatostatin analog can be regarded as the most effective therapy cannot be concluded from the available literature. Also, the development of therapy strategies with combinations of different radionuclides and or peptides is of interest as these strategies may provide an increase in therapeutic efficacy in the future.

Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide.

Peptide receptor scintigraphy with [111In-DTPA-D-Phe1]-octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumours. With this technique primary tumours and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administrations of high doses of [111In-DTPA-D-Phe1]-octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02 to 10 microns and 200 to 500 microns, respectively. Twenty end-stage patients, mostly with neuroendocrine progressing tumours, were treated with [111In-DTPA-D-Phe1]-octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. Results showed there were no major clinical side-effects after up to 2 years treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 16 patients who received a cumulative dose of more than 20 GBq, 5 patients showed stabilisation of disease and 5 other patients a reduction in size of tumours. There is a tendency towards better results in patients whose tumours have a higher accumulation of the radioligand. In conclusion, peptide receptor radionuclide therapy is feasible, also with 111In as radionuclide. Theoretically, depending on the homogeneity of distribution of tumour cells expressing peptide receptors, beta-emitting radionuclides, e.g. 90Y, labelled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]-octreotide started recently.