Preliminary\nStudy of Radionuclide-Labeled MerTK-Targeting\nPET Imaging Agents for the Diagnosis of Melanoma

MerTK PET imaging holds potential as a promising approach\nfor assessing\ntumor aggressiveness and monitoring treatment response. In this study,\nwe synthesized a series of <sup>18</sup>F- and <sup>68</sup>Ga-labeled\ntracers derived from MerTK inhibitors for detection of MerTK expression.\nAmong the synthesized agents, the dimeric compounds [<sup>68</sup>Ga]<b>10</b> and [<sup>68</sup>Ga]<b>12</b> demonstrated\ngood <i>in vivo</i> and <i>in vitro</i> stability,\nhigh affinities to the MerTK receptor, and good MerTK-targeting specificity.\nNotably, [<sup>68</sup>Ga]<b>10</b> exhibited a tumor uptake\nof 2.6 ± 0.2%ID/g at 1 h p. i. in B16F10 tumor-bearing mice,\nnearly tripling the uptake of its monomeric counterpart [<sup>68</sup>Ga]<b>3</b>. A similar enhancement was observed with [<sup>68</sup>Ga]<b>12</b> compared to its monomeric analog [<sup>68</sup>Ga]<b>6</b>. Additionally, [<sup>18</sup>F]<b>14</b> achieved a tumor uptake of 7.6 ± 0.5%ID/g at 2 h p. i., outperforming\nthe previously reported [<sup>18</sup>F]<b>15</b>. Biodistribution\nanalysis further validated the results, highlighting their potential\nfor clinical investigation.