Uptake of radiolabelled endomorphins by experimental mammary adenocarcinoma

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.

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.

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.

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.