Assessing p-Glycoprotein (Pgp) Activity In Vivo Utilizing 68Ga–Schiff Base Complexes

authored by

Marco Fellner, Wolfgang Dillenburg, Hans Georg Buchholz, Nicole Bausbacher, Mathias Schreckenberger, Franz Renz, Frank Rösch, Oliver Thews

Abstract

Purpose: The p-glycoprotein (Pgp) is the most prominent member of active drug transporters leading to a multidrug-resistant phenotype. For identification of tumors functionally overexpressing Pgp in vivo, non-invasive imaging techniques are needed. Procedures: Six Schiff base compounds were synthesized and labeled with ⁶⁸Ge/ ⁶⁸Ga generator-derived ⁶⁸Ga. The compounds were studied in vitro in Pgp-positive tumor cells. The property of being a Pgp substrate was tested by comparison of the tracers uptake in R-3327 Dunning prostate carcinoma AT1 cells in presence and absence of the Pgp-inhibitor verapamil. In vivo investigations were performed with tumor-bearing rats imaged with micro-positron emission tomography. Results: All ligands were labeled with ⁶⁸Ga in yields of 992% beside one (̃55%). The tracers showed different accumulation within the cells in vitro (4-60%). In blocking experiments, the ratio (blocked to unblocked) varied from 1.8 to 1.0. For in vivo experiments, ⁶⁸Ga-ENBDMPI and ⁶⁸Ga-MFL6.MZ were selected. The tumors showed specific uptake of the tracer. Direct intratumoral injection of verapamil increased the tracer concentration by ̃25% reflecting the functional Pgp activity. Conclusions: Two ⁶⁸Ga-labeled ligands appear to be valuable for imaging non-invasively the intratumoral Pgp activity. On a long term, patients with multidrug-resistant tumors pretherapeutically may be identified prior to treatment.

Organisation(s)

Institute of Inorganic Chemistry

External Organisation(s)

Johannes Gutenberg University Mainz

Type

Article

Journal

Molecular imaging and biology

Volume

13

Pages

985-994

No. of pages

10

ISSN

1536-1632

Publication date

10.2011

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Oncology, Radiology Nuclear Medicine and imaging, Cancer Research

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1007/s11307-010-0410-1 (Access: Closed)