Development of a Novel <sup>99m</sup>Tc-Labeled Folate\nDerivative Containing Phenyl Isonitrile to Target Folate Receptor\nwith Reduced Renal Uptake

The\nfolate receptor has attracted much attention in the field of\nradiolabeled imaging agents due to the significant difference in its\nexpression levels between tumor cells and most normal cells. However,\nthe development of folate-based imaging agents has been limited by\ntheir high uptake in the kidney. In this study, to reduce the high\nrenal uptake of radiolabeled folate-based tracers, a phenyl-isonitrile\nfolate derivative (CNMBFA) was designed and labeled with technetium-99m.\nThe complex obtained <i>via</i> the one-step kit labeling\nmethod had a high labeling yield (>95%) and high <i>in vitro</i> stability and hydrophilicity (log <i>D</i><sub>7.4</sub> = −1.72 ± 0.13). The results of the <i>in vitro</i> cell uptake and blocking studies and competitive binding experiments\nrevealed that the [[<sup>99m</sup>Tc]Tc-(CNMBFA)<sub>6</sub>]<sup>+</sup> complex was specific for the folate receptor. Biodistribution\nand inhibition studies in KB tumor-bearing mice revealed moderate\nuptake and significant inhibition of the complex in tumors, whereas\nthe renal uptake of [[<sup>99m</sup>Tc]Tc-(CNMBFA)<sub>6</sub>]<sup>+</sup> was significantly lower than that of previously reported\ntracers. Micro-SPECT/CT images further supported its ability to target\nthe folate receptor for tumor imaging. Taken together, these results\nindicate that [[<sup>99m</sup>Tc]Tc-(CNMBFA)<sub>6</sub>]<sup>+</sup> is a potential tumor imaging agent that has good tumor-targeting\nproperties with minimal radiation damage to the kidney.