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Microwave-assisted One-pot Synthesis of N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB)
Published on: June 28, 2011
18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer
Xianzhong Zhang1, Weibo Cai, Feng Cao
1Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, Stanford, California 94305-5484, USA.
Unlabelled:
The gastrin-releasing peptide receptor (GRPR) is found to be overexpressed in a variety of human tumors. The aim of this study was to develop 18F-labeled bombesin analogs for PET of GRPR expression in prostate cancer xenograft models.
Methods:
[Lys3]Bombesin ([Lys3]BBN) and aminocaproic acid-bombesin(7-14) (Aca-BBN(7-14)) were labeled with 18F by coupling the Lys3 amino group and Aca amino group, respectively, with N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) under slightly basic condition (pH 8.5). Receptor-binding affinity of FB-[Lys3]BBN and FB-Aca-BBN(7-14) was tested in PC-3 human prostate carcinoma cells. Internalization and efflux of both radiotracers were also evaluated. Tumor-targeting efficacy and in vivo kinetics of both radiotracers were examined in male athymic nude mice bearing subcutaneous PC-3 tumors by means of biodistribution and dynamic microPET imaging studies. 18F-FB-[Lys3]BBN was also tested for orthotopic PC-3 tumor delineation. Metabolic stability of 18F-FB-[Lys3]BBN was determined in mouse blood, urine, liver, kidney, and tumor homogenates at 1 h after injection.
Results:
The typical decay-corrected radiochemical yield was about 30%-40% for both tracers, with a total reaction time of 150 +/- 20 min starting from 18F-. 18F-FB-[Lys3]BBN had moderate stability in the blood and PC-3 tumor, whereas it was degraded rapidly in the liver, kidneys, and urine. Both radiotracers exhibited rapid blood clearance. 18F-FB-[Lys3]BBN had predominant renal excretion. 18F-FB-Aca-BBN(7-14) exhibited both hepatobiliary and renal clearance. Dynamic microPET imaging studies revealed that the PC-3 tumor uptake of 18F-FB-[Lys3]BBN in PC-3 tumor was much higher than that of 18F-FB-Aca-BBN(7-14) at all time points examined (P < 0.01). The receptor specificity of 18F-FB-[Lys3]BBN in vivo was demonstrated by effective blocking of tumor uptake in the presence of [Tyr4]BBN. No obvious blockade was found in PC-3 tumor when 18F-FB-Aca-BBN(7-14) was used as radiotracer under the same condition. 18F-FB-[Lys3]BBN was also able to visualize orthotopic PC-3 tumor at early time points after tracer administration, at which time minimal urinary bladder activity was present to interfere with the receptor-mediated tumor uptake.
Conclusion:
This study demonstrates that 18F-FB-[Lys3]BBN and PET are suitable for detecting GRPR-positive prostate cancer in vivo.
Insights
This study developed 18F-FB-[Lys3]BBN, an effective radiotracer for positron emission tomography (PET) imaging. It successfully detected gastrin-releasing peptide receptor (GRPR)-positive prostate cancer in preclinical models.
Area of Science:
- Radiochemistry and Nuclear Medicine
- Oncology
- Molecular Imaging
Background:
- Gastrin-releasing peptide receptor (GRPR) is overexpressed in various human tumors.
- Prostate cancer is a significant health concern with a need for improved diagnostic tools.
Purpose of the Study:
- To develop and evaluate 18F-labeled bombesin analogs for PET imaging of GRPR expression.
- To assess the efficacy of these radiotracers in prostate cancer xenograft models.
Main Methods:
- Radiolabeling of [Lys3]Bombesin and Aca-BBN(7-14) with 18F using 18F-SFB.
- In vitro binding affinity and internalization studies in PC-3 cells.
- In vivo biodistribution and microPET imaging in PC-3 tumor-bearing mice.
Main Results:
- 18F-FB-[Lys3]BBN showed higher tumor uptake and better specificity compared to 18F-FB-Aca-BBN(7-14).
- 18F-FB-[Lys3]BBN demonstrated successful visualization of orthotopic PC-3 tumors with minimal interference.
- The tracer exhibited moderate stability in blood and tumor, with predominantly renal excretion.
Conclusions:
- 18F-FB-[Lys3]BBN is a promising radiotracer for PET detection of GRPR-positive prostate cancer.
- This approach holds potential for non-invasive diagnosis and monitoring of prostate cancer.
