Uptake of radiolabelled endomorphins by experimental mammary adenocarcinoma.

BACKGROUND: The aim of this study was to examine the accumulation of endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin- 2 (Tyr-Pro-Phe-Phe-NH2) labelled with radioiodine in tumour-bearing C3H/Bi mice. MATERIAL AND METHODS: Mice C3H/Bi bearing transplantable mammary adenocarcinoma were used as animal models to study the interaction between micro-opioid receptors and endomorphin-1 and 2. The expression of the micro-opioid receptor in the tumours was confirmed by cross-linking assay and by RT- PCR technique. RESULTS: The endomorphins showed relatively high tumour accumulation - about 5.2% of dose/g tissue for endomorphin-1 and about 3.8% for endomorphin-2. The ratio of tumour to muscle for endomorphin-2 reached the highest value (12.7) six hours after injection. For endomorhin-1 this ratio was the highest (7.5) three hours after injection. The cross-linking assay of [125I]-labelled peptides with membranes, isolated from the mouse adenocarcinoma, followed by electrophoresis and autoradiography revealed the presence of a radioactive complex with molecular weight of about 65 kDa. This complex was detectable by polyclonal antibodies raised against the N-terminal end of a micro-opioid receptor. The expression of gene encoding micro-opioid receptor on mouse mammary adenocarcinoma was further confirmed by RT-PCR technique. The binding studies with membranes of mouse mammary adenocarcinoma cells have shown significantly higher Bmax values for endomorphin-1 and endomorphin- 2 (806 and 671, respectively) than for morphiceptin (131), a well-known specific micro-opioid receptor ligand. CONCLUSIONS: Endomorphin-1 and 2 have shown a high affinity to the m-opioid receptor present in mouse mammary adenocarcinoma. However, endomorphin-2 showed more promising characteristics in biodistribution studies.

Uptake of radiolabelled modified fragment of human alfa-fetoptrotein by experimental mammary adenocarcinoma: in vitro and in vivo studies.

BACKGROUND: The aim of the study was to examine in vitro and in vivo binding of radiolabelled analogues of P149 peptide by experimental mammary adenocarcinoma with the intention of potential application for diagnosis and internal radiotherapy of tumours. MATERIAL AND METHODS: The 36-amino acid peptide (P149-QY) of 90% homology to 447-480 peptide fragment of hAFP was synthesised and radiolabelled with iodine-125. The biodistribution of P149-Q[125I]-Y was studied in experimental mammary tumours. For in vitro experiments, extract from mouse mammary tumours were prepared and incubated with radioiodinated P149-QY peptide in the presence of a cross-linking reagent. RESULTS: The gel electrophoresis analysis (SDS-PAGE) showed that radioiodinated P149-QY peptide formed a complex with adenocarcinoma proteins of about 30 kDa. The biodistribution of P149-Q[125I]-Y studied in experimental mammary tumours revealed a higher pharmacokinetic rate in comparison with the whole radioiodinated AFP molecule. A moderate uptake of P149-Q[125I]-Y in the tumour tissue was observed (3.2% ID/g at 30-min p.i.v). However, a faster radioactivity clearance from blood and normal tissues resulted in an increase in the tumour/muscle (T/M) ratio, i.e. from 2.3 to 3.4 after 30 mins and 24 h p.i.v, respectively. CONCLUSIONS: The present study shows that radioiodinated P149-QY peptide reveals some positive features as the AFP receptor radioligand, however, some additional structural modifications of the initial peptide molecule are necessary for full retention of the ligand-receptor interaction of its radiolabelled forms.

Uptake of radiolabelled herceptin by experimental mammary adenocarcinoma.

BACKGROUND: The aim of this study was to examine the biodistribution of (131)I-herceptin in C3H/Bi mice with transplantable mammary adenocarcinoma with a high frequency of C-erbB2 receptor expression. MATERIAL AND METHODS: Mice C3H/Bi with subcutaneously transplanted mammary adenocarcinoma were used as animal model to study the interaction between C-erbB2 receptor and hercepin, a humanized anti-C-erbB2 monoclonal antibody. The expression of the gene encoding C-erbB2 receptor in the tumours was studied by the RT-PCR technique. RESULTS: Expression of this gene was found in 66% of the studied cases. Similarly, the presence of the C-erbB2 receptor in 77% of the tumours was detected by a Western blot analysis with the use of herceptin. Biodistribution experiments of iodine-labelled herceptin in mice C3H/Bi with adenocarcinoma revealed its maximal accumulation in the tumours at 48 hours since the i.v. injection (7% ID/g). The tumour/muscle radioactivity ratio reached its highest value (above 20) also at 48 hours after the injection. CONCLUSIONS: C3H/Bi mice with this adenocarcinoma may be a good experimental model to study herceptin, or its fragments, labelled with different radionuclids for preliminary evaluation of their usefulness in the therapeutic and diagnostic aspects of breast cancer.

Biological investigation of the platinum(II)-[*I]iodohistamine complexes of potential synergistic anti-cancer activity.

Cisplatin chemotherapy in combination with external irradiation or with low-dose continuous internal radiotherapy produces significant supra-additive treatment effects towards several tumor cells. The purpose of our research is to develop a new class of platinum-based anticancer drugs containing moieties of synergistic potency such as platinum core and a radiotherapeutic isotope which, delivered directly to the tumorous cells by a specifically designed vectors, should produce a local enhancement of therapeutic dose. Thus, we have synthesized a new platinum-iodohistamine complex and its radioactive analogues labeled with I-125 and I-131. In the present study some biological properties of those compounds have been investigated. The in vitro screening study pointed out that non-radioactive platinum-iodohistamine complex possesses high cytostatic activity against COLO-205 cells, and moderate activity against HL-60 cell line. No cytotoxicity was observed against MOLT-4 and L-1210 cells, as well as against VERO normal cells. The biodistribution of intravenously administered radioactive platinum-[131I]-iodohistamine complex to normal rats revealed the highest accumulation in the liver (c.a. 40%ID). Intraperitoneal injections of the complex to tumor-bearing C3H mice resulted in scattering of the dose in the organs (mainly in GIT, liver, kidney). The retention of radioactive complex in neoplastic tissue was 3-4 times higher than in normal muscular tissue, although exhibited the tendency to decrease with time post injection. The results of the present study show promising features of the newly developed platinum-iodohistamine complexes and justify prospective investigation of in vivo anticancer potency on animal models of solid tumors.