Objective To investigate the differences in the nonspecific uptake of Al¹⁸F-prostate specific membrane antigen (PSMA)-3Q prepared by column chromatography and high performance liquid chromatography (HPLC) in PET/CT imaging and evaluate its effect on the accuracy of PSMA expression score.

Methods A retrospective inclusion was conducted on 52 prostate disease patients (age (69.5±8.1) years) who underwent Al¹⁸F-PSMA-3Q (synthesized by column chromatography) PET/CT imaging (column chromatography group) and 54 prostate disease patients (age (70.0±9.2) years) who underwent Al¹⁸F-PSMA-3Q (synthesized by HPLC) PET/CT imaging (HPLC group) at the First Medical Center of Chinese PLA General Hospital between July 2021 and January 2024. The maximum standardized uptake value (SUV_max) and mean standardized uptake value (SUV_mean) of the reference organs for PSMA expression score (aortic arch blood pool, parotid gland, and liver) were measured, and nonspecific uptake situations, including all focal or diffuse uptake that showed no clear association with known prostate diseases except for physiological uptake sites (salivary glands, lacrimal glands, nasal cavity, nasopharynx, liver, spleen, kidneys, small intestine, ganglia, etc.), were recorded. Independent samples t-test, Welch′s corrected t-test, or Mann-Whitney U test was used for intergroup comparison of measurement data; chi-square test was used for comparison of count data between groups.

Results The Al¹⁸F-PSMA-3Q prepared by both methods had a radiochemical purity >95%, and the free ¹⁸F⁻ content was <1%. No statistically significant differences were observed in the incidence of nonspecific uptake between the two groups (bones: 15.4% vs. 16.7%, χ²=0.032, P=0.857; axillary lymph nodes: 9.6% vs. 9.3%, χ²=0.004, P=0.950; epididymis: 5.8% vs. 5.6%, χ²=0.002, P=0.962; main bronchi: 5.8% vs. 3.7%, χ²=0.251, P=0.616; breast: 3.8% vs. 3.7%, χ²=0.001, P=0.969; subcutaneous tissue: 1.9% vs. 3.7%, χ²=0.305, P=0.581; bone marrow: 1.9% vs. 1.9%, χ²=0.001, P=0.979; lung parenchyma: 1.9% vs. 0, χ²=1.048, P=0.306). The column chromatography group displayed higher SUV_max and SUV_mean of the aortic arch blood pool compared with the HPLC group (SUV_max: 1.63±0.44 vs. 1.45±0.28, t=2.546, P=0.012; SUV_mean: 1.42±0.42 vs. 1.24±0.26, t=2.698, P=0.008).

Conclusions Bones represent the most common sites of nonspecific uptake in Al¹⁸F-PSMA-3Q PET/CT imaging. Although the two methods do not change the incidence of nonspecific uptake in Al¹⁸F-PSMA-3Q PET/CT imaging, column chromatography may lead to an increase in blood pool background uptake, which potentially affects the accurate evaluation of lesions with a low PSMA expression score.