Anti-proliferative effect of radiolabelled octreotide in a metastases model in rat liver

Most neuroendocrine tumours and several other tumours, such as breast carci noma and malignant lymphoma, express somatostatin receptors (SS-Rs). Lesion s expressing these receptors can be visualised by receptor scintigraphy usi ng a low radioactive dose of the radiolabelled SS analogue [In-111-DTPA(0)] octreotide. This radioligand is internalised and transported to the lysosom es with a long residence time of (111)ln. The aim of this experimental stud y in rats was to investigate whether the same agent, given in a high radioa ctive dose, can be used for therapy of hepatic metastases of different tumo ur 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 I and/or 8, animals were treated with 370 MBq ( 0.5 mu g) [(111)ln-DTPA(0)]octreotide. In one experiment, using SS-R-positi ve tumour cells, animals were pre-treated with a high dose of cold octreoti de to block the SS-R by saturation. The number of SS-R-positive liver metas tases was significantly decreased after treatment with [(111)ln-DTPA(0)]oct reotide. Blocking the SS-R by octreotide substantially decreased the effica cy of treatment with [(111)ln-DTPA(0)]octreotide, suggesting that the prese nce 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 [(111 )ln-DTPA(0)]octreotide. Therefore, we conclude that (i) high radioactive do ses of [In-111-DTPA(0)]octreotide for PRRT (peptide receptor radionuclide t herapy) can inhibit the growth of SS-R-positive liver metastases in an anim al model, (ii) PRRT is effective only if SS-Rs are present on the tumours, (iii) the effect of PRRT with [(111)ln-DTPA(0)]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 octreo tide might be a new promising treatment modality for SS-R-positive tumours. Int. j. Cancer 81:767-771, 1999. (C) 1999 Wiley-Liss, Inc.