PET study on mice bearing human colon adenocarcinoma cells using [11C]GF120918, a dual radioligand for P-glycoprotein and breast cancer resistance protein.

Abstract

OBJECTIVE:

To evaluate the functions of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) in human colon adenocarcinoma (Caco-2), we carried out an in-vitro study and a small animal positron emission tomography (PET) study using [C]GF120918 (elacridar).

METHODS:

[C]GF120918 was synthesized by reacting the desmethyl precursor with [C]CH3I. An in-vitro study using [C]GF120918 was carried out in Caco-2 and Madin-Darby canine kidney cells in the presence or absence of a transporter inhibitor (cyclosporine A and unlabeled GF120918). The biodistribution of radioactivity after the injection of [C]GF120918 was determined in Caco-2-bearing mice using a small animal PET scanner.

RESULTS:

In Caco-2 cells expressing Pgp and BCRP, coincubation with unlabeled GF120918 caused an approximately two-fold increase in [C]GF120918 uptake compared with that of the control ([C]GF120918 only). In Caco-2-bearing mice, PET results indicated that [C]GF120918 uptake in the tumor was low, but was significantly increased by treatment with unlabeled GF120918. In metabolite analysis, the radioactive component in the tumor almost corresponded to intact [C]GF120918.

CONCLUSION:

A PET study combining the administration of [C]GF120918 with unlabeled GF120918 may be a useful tool for evaluating the functions of Pgp and BCRP in tumors.

• Authors: Tomoteru Yamasaki, Kazunori Kawamura, Akiko Hatori, Joji Yui, Kazuhiko Yanamoto, Yuichiro Yoshida, Masanao Ogawa, Nobuki Nengaki, Hidekatsu Wakisaka, Toshimitsu Fukumura, Ming-Rong Zhang
• Journal: Nuclear medicine communications (Nucl Med Commun) Vol. 31 Issue 11 Pg. 985-93 (Nov 2010) ISSN: 1473-5628 [Electronic] England
• PMID: 20859232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Acridines
• Carbon Radioisotopes
• Ligands
• Neoplasm Proteins
• Tetrahydroisoquinolines
• Elacridar

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (metabolism)
• Acridines (metabolism)
• Adenocarcinoma (pathology)
• Animals
• Biological Transport
• Blotting, Western
• Caco-2 Cells
• Carbon Radioisotopes
• Colonic Neoplasms (pathology)
• Dogs
• Humans
• Ligands
• Male
• Mice
• Neoplasm Proteins (metabolism)
• Positron-Emission Tomography (methods)
• Tetrahydroisoquinolines (metabolism)
• Tomography, Emission-Computed, Single-Photon