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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.

Peptide receptor scintigraphy with the radioactive somatostatin analogue, [111In-DTPA0]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 (PRRT) with repeated administrations of high doses of [111In-DTPA0)octreotide. 111In emits Auger and conversion electrons having a tissue penetration of 0.02-10 microns and 200 to 500 microns, respectively. Thirty end-stage patients with mostly neuroendocrine progressing tumours were treated with [111In-DTPA0]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase I trial. There were no major clinical side effects after up to two years treatment, except that in a few patients a transient decline in platelets counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production and tumour proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight patients showed stabilisation of disease and six 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. PRRT is feasible, also with 111In as radionuclide. Depending on the homogeneity of distribution of tumour cells expressing peptide receptors and the size of the tumour, beta-emitting radionuclides, e.g., 90Y, labelled to DOTA-chelated peptides, are also attractive candidates for PRRT. The first PRRT trials with [90Y-DOTA0,Tyr3]octreotide started recently.

A case of antibody formation in a patient with carcinoid syndrome is described. The patient was treated with octreotide in dosages up to 1.5 mg/day. Serum samples were analysed for the presence of octreotide antibodies before and after 20 months of octreotide treatment. In-vivo 111In-octreotide scintigraphy was performed before and during therapy, and after antibodies had developed. Before treatment, no serum antibodies against octreotide were detected. After 20 months of treatment, they were detectable up to a 1:115 serum dilution. The serum binding of 125I-Tyr3-octreotide was blocked by adding excess unlabelled Tyr3-octreotide, indicating the presence of specific octreotide antibodies. Before treatment, a normal distribution of radioactivity in the spleen and kidneys, irregular uptake in the liver due to metastases, and a hot spot in the lower abdomen were found during 111In-octreotide scintigraphy. After antibodies had developed, increased radioactivity over the heart and high background radioactivity in the abdomen with only faint visualization of the spleen, liver, and kidneys were found, indicating a prolonged presence of 111In-octreotide in the blood resulting from its being bound to antibodies. Increased radioactivity was also seen at the injection sites of the drug in the upper legs. In-vitro incubation of biopsy tissue from this site with 125I-Tyr3-octreotide revealed diffuse guanosine triphosphate (GTP) independent specific binding non-G-protein linked binding of labelled octreotide. This report describes the characteristic abnormalities during in-vivo 111In-octreotide scintigraphy in a patient with octreotide antibodies. These consisted of high background radioactivity due to prolonged circulation of antibody coupled 111In-octreotide together with visualization of the injection sites, which most probably results from local accumulation of anti