Details
| Original language | English |
|---|---|
| Pages (from-to) | 985-994 |
| Number of pages | 10 |
| Journal | Molecular imaging and biology |
| Volume | 13 |
| Issue number | 5 |
| Early online date | 8 Sept 2010 |
| Publication status | Published - Oct 2011 |
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.
Keywords
- Ga, Functional activity, P-glycoprotein, PET tracer, Tumors
ASJC Scopus subject areas
- Medicine(all)
- Oncology
- Medicine(all)
- Radiology Nuclear Medicine and imaging
- Biochemistry, Genetics and Molecular Biology(all)
- Cancer Research
Sustainable Development Goals
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In: Molecular imaging and biology, Vol. 13, No. 5, 10.2011, p. 985-994.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Assessing p-Glycoprotein (Pgp) Activity In Vivo Utilizing 68Ga–Schiff Base Complexes
AU - Fellner, Marco
AU - Dillenburg, Wolfgang
AU - Buchholz, Hans Georg
AU - Bausbacher, Nicole
AU - Schreckenberger, Mathias
AU - Renz, Franz
AU - Rösch, Frank
AU - Thews, Oliver
N1 - Funding Information: Acknowledgments. The study was supported by the European Union (project COST D38 and BM0607) and the Deutsche Krebshilfe (grant 109136).
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - Ga
KW - Functional activity
KW - P-glycoprotein
KW - PET tracer
KW - Tumors
UR - http://www.scopus.com/inward/record.url?scp=84855659651&partnerID=8YFLogxK
U2 - 10.1007/s11307-010-0410-1
DO - 10.1007/s11307-010-0410-1
M3 - Article
C2 - 20824508
AN - SCOPUS:84855659651
VL - 13
SP - 985
EP - 994
JO - Molecular imaging and biology
JF - Molecular imaging and biology
SN - 1536-1632
IS - 5
ER -