期刊论文详细信息
The Journal of Nuclear Medicine
A Radiotracer for Molecular Imaging and Therapy of Gastrin-Releasing Peptide Receptor–Positive Prostate Cancer
article
Ivica J. Bratanovic1  Chengcheng Zhang1  Zhengxing Zhang1  Hsiou‐Ting Kuo1  Nadine Colpo1  Jutta Zeisler1  Helen Merkens1  Carlos Uribe2  Kuo‐Shyan Lin1  François Bénard1 
[1] BC Cancer;Department of Radiology, University of British Columbia;Functional Imaging
关键词: gastrin-releasing peptide receptor;    bombesin;    prostate cancer;   
DOI  :  10.2967/jnumed.120.257758
学科分类:医学(综合)
来源: Society of Nuclear Medicine
PDF
【 摘 要 】

The gastrin-releasing peptide receptor (GRPR) is overexpressed in many solid malignancies, particularly in prostate and breast cancers, among others. We synthesized ProBOMB2, a novel bombesin derivative radiolabeled with 68Ga and 177Lu, and evaluated its ability to target GRPR in a preclinical model of human prostate cancer. Methods: ProBOMB2 was synthesized in solid phase using fluorenylmethoxycarbonyl chemistry. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was coupled to the N terminus and separated from the GRPR-targeting sequence by a cationic 4-amino-(1-carboxymethyl)-piperidine spacer. Binding affinity for both human and murine GRPR was determined using a cell-based competition assay, whereas a calcium efflux assay was used to measure the agonist and antagonist properties of the derivatives. ProBOMB2 was radiolabeled with 177Lu and 68Ga. SPECT and PET imaging and biodistribution studies were conducted using male immunocompromised mice bearing GRPR-positive PC-3 human prostate cancer xenografts. Results: Ga-ProBOMB2 and Lu-ProBOMB2 bound to PC-3 cells with an inhibition constant of 4.58 ± 0.67 and 7.29 ± 1.73 nM, respectively. 68Ga-ProBOMB2 and 177Lu-ProBOMB2 were radiolabeled with a radiochemical purity greater than 95%. Both radiotracers were excreted primarily via the renal pathway. PET images of PC-3 tumor xenografts were visualized with excellent contrast at 1 and 2 h after injection with 68Ga-ProBOMB2, and there was very low off-target organ accumulation. 177Lu-ProBOMB2 enabled clear visualization of PC-3 tumor xenografts by SPECT imaging at 1, 4, and 24 h after injection 177Lu-ProBOMB2 displayed higher tumor uptake than 68Ga-ProBOMB2 at 1 h after injection. 177Lu-ProBOMB2 tumor uptake at 1, 4, and 24 h after injection was 14.9 ± 3.1, 4.8 ± 2.1, and 1.7 ± 0.3 percentage injected dose per gram of tissue, respectively. Conclusion: 68Ga-ProBOMB2 and 177Lu-ProBOMB2 are promising radiotracers with limited pancreas uptake, good tumor uptake, and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.

【 授权许可】

CC BY   

【 预 览 】
附件列表
Files Size Format View
RO202307060003959ZK.pdf 987KB PDF download
  文献评价指标  
  下载次数:1次 浏览次数:1次