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 µ-opioid receptors and endomorphin-1 and 2. The expression of the µ-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 µ-opioid receptor. The expression of gene encoding µ-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 B_max values for endomorphin-1 and endomorphin- 2 (806 and 671, respectively) than for morphiceptin (131), a well-known specific µ-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.