18F-labeled bombesin analog for specific and effective targeting of prostate tumors expressing gastrin-releasing peptide receptors.

Abstract

UNLABELLED:

Bombesin is a peptide exhibiting high affinity for the gastrin-releasing peptide receptor (GRPr), which is highly overexpressed on prostate cancer cells. In the present study, we developed an (18)F-labeled bombesin analog, (18)F-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer.

METHODS:

In vitro pharmacologic studies were performed to characterize the nonradioactive ((19)F) standard of the bombesin analog for binding affinity and selectivity for GRPr. The stability of (18)F-BAY 86-4367 was determined in murine and human plasma. In vivo, the tumor-targeting potential and pharmacokinetic profile of the (18)F tracer were analyzed with biodistribution experiments and PET studies of prostate tumor-bearing mice.

RESULTS:

The nonradioactive ((19)F) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability of the tracer in murine and human plasma was found to be high. In 2 prostate cancer xenograft models (PC-3 and LNCaP), (18)F-BAY 86-4367 showed more specific and effective GRPr-based targeting in vivo than the benchmark radiotracers (18)F-fluoroethylcholine and (18)F-FDG. In addition, rapid tumor targeting and fast renal excretion (∼70%) and hepatobiliary excretion (∼10%) were identified in both xenograft models. Furthermore, PET studies provided clear and specific visualization of PC-3 tumors in mice.

CONCLUSION:

Favorable preclinical data showing specific and effective tumor targeting by (18)F-BAY 86-4367 suggest that a clinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.

• Authors: Michael Honer, Linjing Mu, Timo Stellfeld, Keith Graham, Miljen Martic, Cindy R Fischer, Lutz Lehmann, Pius A Schubiger, Simon M Ametamey, Ludger Dinkelborg, Ananth Srinivasan, Sandra Borkowski
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 52 Issue 2 Pg. 270-8 (Feb 2011) ISSN: 1535-5667 [Electronic] United States
• PMID: 21233180 (Publication Type: Journal Article)

Chemical References

• BAY 86-4367
• Fluorine Radioisotopes
• Indicators and Reagents
• Radiopharmaceuticals
• Receptors, Bombesin
• Cysteic Acid
• Bombesin

Topics

• Animals
• Binding, Competitive (drug effects)
• Bombesin (analogs & derivatives, chemistry, pharmacokinetics)
• Cell Line
• Cysteic Acid (chemistry)
• Drug Stability
• Fluorine Radioisotopes
• Humans
• Indicators and Reagents
• Isotope Labeling
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Prostatic Neoplasms (diagnostic imaging, metabolism)
• Radionuclide Imaging
• Radiopharmaceuticals (chemistry, pharmacokinetics)
• Receptors, Bombesin (genetics, metabolism)
• Tissue Distribution