Promising potential of a 18F-labelled small-molecular radiotracer to evaluate PD-L1 expression in tumors by PET imaging

Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer

“…2 C). Compared with similar tracers 124 I-anti-hPD-L1 Nb6 ( K D = 2.19 nM) [ 39 ] and [ 18 F]LG-1 ( K D = 63.13 nM) [ 40 ], ours showed a higher affinity for PD-L1. The saturation assay proved that site-specific conjugation did not alter the characteristics of single-domain antibody and that the tracer still had a strong affinity for PD-L1.…”

Development of Radiotracers for Imaging of the PD-1/PD-L1 Axis

“…So far, only one small molecule PD-L1 inhibitor has been radiofluorinated by employing an 18 F- 19 F isotope exchange on an alkylammoniomethyltrifluoroborate (AMBF3) moiety (see compound 3 in Figure 11 above) [64]. Because the radioligand was very lipophilic and exhibited a high liver uptake, another more hydrophilic radioligand bearing a 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) moiety was synthesized from the same parent molecule [65].…”

“…[ 68 Ga]Ga-NJMP1 68 Ga PET 25.9 µM [63] Small Molecule [ 18 F]FLN 18 F PET 65.3 nM [64] [ 18 F]FLG-1 18 F 63.1 nM [65] HAC-PD1 DOTA-HAC 64 Cu PET ~110 pM [66] NOTA-HAC NOTA-HACA DOTA-HACA 1 Values for non-conjugated Atezolizumab. 2 Value for unsubstituted peptide; K D for substituted peptide was found to be in the same range.…”

“…Due to this low molecular weight, they exhibit a higher oral bioavailability and a faster clearance, and they can be readily upscaled to save costs for institutions, patients, and society as a whole [101]. Despite the report of several organic small molecules inhibiting the PD-1/PD-L1 pathway [102][103][104], only two small molecule-based PET tracers have been published so far (Figure 11) [64,65]. Reprinted/adapted with permission from Ref.…”

“…revealed higher uptakes in the kidneys and liver compared to the tumor uptake. Due to the lipophilicity of the radioligand, they tried to optimize the radioligand by using the hydrophilic 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) moiety as a radiolabel and to reduce the overall lipophilicity (compound 4) [65]. This resulted in a reduced liver uptake and an improved imaging contrast.…”