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.

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See also:

- Somatostatin in oncology, the overlooked evidences;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.