title: Anti-proliferative effect of radiolabelled octreotide in a metastases model in rat liver.
abstract: Most neuroendocrine tumours and several other tumours, such as breast carcinoma and malignant lymphoma, express somatostatin receptors (SS-Rs). Lesions expressing these receptors can be visualised by receptor scintigraphy using a low radioactive dose of the radiolabelled SS analogue [111In-DTPA0]octreotide. This radioligand is internalised and transported to the lysosomes with a long residence time of 111In. The aim of this experimental study in rats was to investigate whether the same agent, given in a high radioactive dose, can be used for therapy of hepatic metastases of different tumour cell lines. The development of hepatic metastases was determined 21 days after direct injection of SS-R-positive or -negative tumour cells into the vena porta in rats. On day 1 and/or 8, animals were treated with 370 MBq (0.5 microg) [111In-DTPA0]octreotide. In one experiment, using SS-R-positive tumour cells, animals were pre-treated with a high dose of cold octreotide to block the SS-R by saturation. The number of SS-R-positive liver metastases was significantly decreased after treatment with [111In-DTPA0]octreotide. Blocking the SS-R by octreotide substantially decreased the efficacy of treatment with [111In-DTPA0]octreotide, suggesting that the presence of SS-R is mandatory. This was confirmed by the finding that the number of SS-R-negative liver metastases was not affected by treatment with [111In-DTPA0]octreotide. Therefore, we conclude that (i) high radioactive doses of [111In-DTPA0]octreotide for PRRT (peptide receptor radionuclide therapy) can inhibit the growth of SS-R-positive liver metastases in an animal model, (ii) PRRT is effective only if SS-Rs are present on the tumours, (iii) the effect of PRRT with [111In-DTPA0]octreotide can be reduced by pre-treatment with cold octreotide, which indicates that receptor binding is essential for PRRT. Our data suggest that PRRT with radiolabelled octreotide might be a new promising treatment modality for SS-R-positive tumours.
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D007205:Indium Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D017481:Receptors, Somatostatin / Q000378:metabolism; D014407:Tumor Cells, Cultured