Abstract

Purpose The aim of this study was to explore an effective 124 I labeling strategy and improve the signal-to-noise ratio when evaluating the expression of PD-L1 using an 124 I-iodinated durvalumab (durva) F(ab') 2 fragment. Methods The prepared durva F(ab') 2 fragments were incubated with N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP); after purification, the HPP-durva F(ab') 2 was iodinated using Iodo-Gen method. After the radiochemical purity, stability, and specific activities were determined, the binding affinities of probes prepared using different labeling strategies were compared in vitro. The clinical application value of [ 124 I]I-HPP-durva-F(ab') 2 was confirmed by PET imaging. To more objectively evaluate the in vivo distribution and clearance of tracers, the pharmacokinetics and biodistribution assays were also performed. Results After being modified with SHPP, the average conjugation number of SHPP per durva-F(ab') 2 identified by LC–MS was about 8.92 ± 2.84. The prepared [ 124 I]I-HPP-durva F(ab') 2 was obtained with a satisfactory radiochemical purity of more than 98% and stability of more than 93% when incubated for 72 h. Compared with unmodified [ 124 I]I-durva F(ab') 2 , the specific activity of [ 124 I]I-HPP-durva-F(ab') 2 was improved (52.91 ± 5.55 MBq/mg and 15.91 ± 0.74 MBq/mg), while the affinity did not significantly change. The biodistribution experiments and PET imaging showed that the prepared [ 124 I]I-HPP-durva-F(ab') 2 exhibited an accelerated clearance and improved tumor-to-background ratio compared with [ 124 I]I-durva-F(ab') 2 . The specificity of [ 124 I]I-HPP-durva-F(ab') 2 to PD-L1 was well demonstrated both in vitro and in vivo. Conclusions A PD-L1 PET imaging probe [ 124 I]I-HPP-durva F(ab') 2 was successfully synthesized through the SHPP modification strategy. The prepared probe was able to accurately evaluate the PD-L1 expression level through high-contrast noninvasive imaging.