Gastrin-releasing peptide receptor targeted PET imaging of 68Ga-DOTA-PEG 4-BBN for prostate cancer
10.3760/cma.j.cn321828-20231106-00097
- VernacularTitle:靶向前列腺癌胃泌素释放肽受体 68Ga-DOTA-PEG 4-BBN PET显像研究
- Author:
Jiaqi YUAN
1
;
Yaxi LI
;
Dujuan LIU
;
Ran REN
;
Menglu LI
;
Ninghan FENG
;
Jianming NI
Author Information
1. 南京医科大学附属无锡第二医院影像科，无锡 214002
- Keywords:
Prostatic neoplasms;
Receptors, bombesin;
Isotope labeling;
Gallium radioisotopes;
Positron-emission tomography;
Mice, nude
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2024;44(5):303-308
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To design and develop a molecular imaging probe of 68Ga-labeled bombesin (BBN) analogue, 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-polyethylene glycol (PEG) 4-BBN, and investigate its potential to target prostate cancer with high expression of gastrin-releasing peptide receptor (GRPR) while minimizing uptake in pancreatic tissue. Methods:Based on the amino acid sequence of BBN peptides, the precursor DOTA-PEG 4-BBN was designed and prepared, followed by labeling with 68Ga and conducting to quality control analysis. The tumor uptake of 68Ga-DOTA-PEG 4-BBN was assessed by microPET/CT imaging on tumor-bearing nude mice models with PC3 of high GRPR expression or HT29 of low GRPR expression (3 mice per group). 68Ga-DOTA-PEG 4-BBN microPET/CT imaging was also performed on 6 tumor-bearing nude mice models with PC3, among which 3 mice were treated with gastrin-releasing peptide antagonist 1 h prior to injection of the tracer (blocked group). After imaging, the ex vivo tissues of 3 PC3 tumor-bearing nude mice of the non-blocked group were examined for radioactivity counting to evaluation the biodistribution of 68Ga-DOTA-PEG 4-BBN, and the percentage injected dose per gram of tissue (%ID/g) was calculated. Independent-sample t test was used for data analysis. Results:The synthesis of 68Ga-DOTA-PEG 4-BBN took 40 min, with the radiochemical yield of 50%-60% (no decay correction) and the radiochemical purity of over 95%. After incubation in the serum at 37 ℃ for 4 h, the radiochemical purity remained more than 95%. The microPET/CT imaging results indicated that the uptake in the PC3 tumor was 3.2 times higher than the uptake in the tumor after GRPR blockade ((1.34±0.24) vs (0.42±0.03) %ID/g; t=5.47, P=0.005). After the injection of 68Ga-DOTA-PEG 4-BBN at 1 h and following imaging for 15 min, the PC3 tumor-bearing nude mice models of the non-blocked group showed that the pancreatic uptake ((0.150±0.058) %ID/g) was significantly lower than that in kidneys, lungs and liver ((9.452±0.234), (0.720±0.041), (1.572±0.213) %ID/g) with a profound statistical distinction ( t values: 11.28-53.02, all P<0.001). The tumor/pancreas uptake ratio could reach 16.92 in the tumor-bearing nude mice models with high GRPR expression. Conclusion:A novel molecular imaging probe 68Ga-DOTA-PEG 4-BBN demonstrates specific recognition of tumors with high GRPR expression while exhibiting low uptake in the pancreas, which shows its potential in prostate cancer molecular imaging.
