Comparison of renal clearance of [ 18 F]AlF-RESCA-HER2-BCH and [ 18 F]AlF-NOTA-HER2-BCH in mice and breast cancer patients

European journal of nuclear medicine and molecular imaging(2023)

Cited 0|Views23
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Abstract
Purpose A novel HER2 affibody-based molecular probe, [ 18 F]AlF-RESCA-HER2-BCH, was developed for reducing renal uptake, evaluated, and compared with [ 18 F]AlF-NOTA-HER2-BCH. Methods In preclinical studies, micro-PET/CT was performed using HER2-positive gastric cancer patient-derived xenografts (PDX) model at 0.5-1 (dynamic), 2, 4, and 6 h post-injection. For blocking experiment, 0.5 mg cold affibody was co-injected with probes. Biodistribution were performed on HER2-positive PDX models at 2 h post-injection. For clinical study, PET/CT images were acquired at 2 h and 4 h after injection of 231.29 ± 17.77 MBq [ 18 F]AlF-NOTA-HER2-BCH or [ 18 F]AlF-RESCA-HER2-BCH in five breast cancer patients (4 HER2-positive and 1 HER2-low). Standardized uptake values (SUVs) were measured in tumors and source-organs for semi-quantitative analysis. The OLINDA/EXM software (version 1.2) was used to calculate the radiation doses. Results [ 18 F]AlF-NOTA-HER2-BCH and [ 18 F]AlF-RESCA-HER2-BCH were stably labeled with [ 18 F]F, with high binding specificity and affinity to HER2. Micro-PET/CT of both tracers could clearly visualize HER2-positive PDX tumors with high uptake of 16.24 ± 1.74% ID/g and 14.39 ± 2.45% ID/g at 2 h post-injection. The renal accumulation of [ 18 F]AlF-RESCA-HER2-BCH was significantly lower than that of [ 18 F]AlF-NOTA-HER2-BCH (5.16 ± 0.22% ID/g vs. 158.73 ± 5.44% ID/g at 2 h, p < 0.0001). In the clinical study, both [ 18 F]AlF-NOTA-HER2-BCH and [ 18 F]AlF-RESCA-HER2-BCH demonstrated favorable tumor targeting and image contrast. [ 18 F]AlF-RESCA-HER2-BCH showed a higher SUVmax in both primary tumor and metastases, and a significantly higher target-to-nontarget ratio in metastases than [ 18 F]AlF-NOTA-HER2-BCH. Moreover, [ 18 F]AlF-RESCA-HER2-BCH had lower renal accumulation (43.56 ± 7.88 vs. 79.81 ± 3.81 at 2 h, p < 0.0001; 33.23 ± 6.89 vs. 78.63 ± 4.00 at 4 h, p < 0.0001) as well as a significantly lower renal absorbed dose than [ 18 F]AlF-NOTA-HER2-BCH (0.4450 ± 0.1117 mGy/MBq vs. 0.8030 ± 0.1604 mGy/MBq, p < 0.01). Conclusions [ 18 F]AlF-RESCA-HER2-BCH tended to provide better image contrast than [ 18 F]AlF-NOTA-HER2-BCH with a higher target-to-nontarget ratio in detection of metastases. Notably, [ 18 F]AlF-RESCA-HER2-BCH had lower renal accumulation than [ 18 F]AlF-NOTA-HER2-BCH.
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Key words
Fluorine-18 labeling,HER2 affibody,PET/CT,[18F]AlF-NOTA-HER2-BCH,[18F]AlF-RESCA-HER2-BCH
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