Anti-proliferative effect of radiolabelled octreotide in a metastases model in rat liver
β Scribed by Gerrit D. Slooter; Wouter A.P. Breeman; Richard L. Marquet; Eric P. Krenning; Casper H.J. van Eijck
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 186 KB
- Volume
- 81
- Category
- Article
- ISSN
- 0020-7136
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β¦ Synopsis
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 [ 111 In-DTPA 0 ]octreotide. This radioligand is internalised and transported to the lysosomes with a long residence time of 111 In. 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 Β΅g) [ 111 In-DTPA 0 ]octreotide. In one experiment, using SS-Rpositive 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 [ 111 In-DTPA 0 ]octreotide. Blocking the SS-R by octreotide substantially decreased the efficacy of treatment with [ 111 In-DTPA 0 ]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 [ 111 In-DTPA 0 ]octreotide. Therefore, we conclude that (i) high radioactive doses of [ 111 In-DTPA 0 ]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 [ 111 In-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 octreotide might be a new promising treatment modality for SS-R-positive tumours. Int.
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