Uptake of radiolabelled endomorphins by experimental mammary adenocarcinoma.

Abstract

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.

• Authors: Rafał Wiercioch, Marek Mirowski, Ewa Balcerczak, Ewa Byszewska, Ryszard Wierzbicki
• Journal: Nuclear medicine review. Central & Eastern Europe (Nucl Med Rev Cent East Eur) Vol. 8 Issue 1 Pg. 1-5 ( 2005) ISSN: 1506-9680 [Print] Poland
• PMID: 15977139 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cross-Linking Reagents
• Iodine Radioisotopes
• Ligands
• Oligopeptides
• Peptides
• Receptors, Opioid, mu
• endomorphin 1
• endomorphin 2

Topics

• Adenocarcinoma (pathology)
• Animals
• Autoradiography
• Cell Membrane (metabolism)
• Cross-Linking Reagents (pharmacology)
• Female
• Iodine Radioisotopes (pharmacokinetics)
• Kinetics
• Ligands
• Mammary Neoplasms, Experimental (pathology)
• Mice
• Mice, Inbred C3H
• Neoplasm Transplantation
• Oligopeptides (pharmacokinetics)
• Peptides (chemistry)
• Protein Binding
• Receptors, Opioid, mu (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Tissue Distribution