Objectives:　Tumor　heterogeneity　and　acquired　resistance　to　prostate-specific　membrane　antigen　(PSMA)　radioligand　therapy　(PRLT)　pose　significant　challenges　to　PSMA　PET-based　diagnosis.　This　study　aimed　to　develop　an　(AlF)-F-18-labeled　FAP-targeted　tracer　and　explore　the　diagnostic　value　in　acquired　drug-resistant　tumor　models.　Methods:　To　identify　potential　targets　for　imaging　drug-resistant　prostate　cancer,　bioinformatic　analysis　was　employed　to　correlate　FAP　expression　levels　with　genes　associated　with　tumor　progression　and　radiotherapy　resistance.　Molecular　docking　technology　simulations　were　utilized　to　screen　FAP　ligands　for　optimal　binding　affinity　and　target　specificity.　The　most　promising　ligand,　FAP-2286,　was　radiolabeled　with　F-18　to　develop　a　novel　PET　imaging　agent,　(AlF)-F-18-NOTA-FAP-2286　PET.　To　evaluate　the　diagnostic　potential　of　this　agent,　various　tumor　models　were　established.　U87　cells　were　used　to　optimize　the　imaging　protocol　and　assess　targeting　efficiency　and　22RV-1-resistant　cells　co-xenografted　with　NIH-3T3　cells　were　used　to　model　acquired　drug-resistant　prostate　cancer.　The　diagnostic　efficacy　of　(AlF)-F-18-NOTA-FAP-2286　PET　in　this　acquired　drug-resistant　model　was　assessed　and　validated　through　immunohistochemical　staining　of　tumor　tissue.　Results:　Bioinformatic　analysis　confirmed　the　association　between　FAP　expression　and　key　genes　involved　in　radiotherapy　resistance,　such　as　HIF1　alpha,　BCL2,　ATM,　and　EGFR.　Molecular　docking　studies　demonstrated　the　strong　binding　affinity　of　FAP-2286　to　FAP　alpha　(-10　kcal/mol).　(AlF)-F-18-NOTA-FAP-2286　PET/CT　imaging　in　U87　tumor-bearing　mice　revealed　accurate　targeting　of　high　FAP-expressing　xenografts.　The　imaging　characteristics　of　(AlF)-F-18-NOTA-FAP-2286　were　comparable　to　F-18-FDG　and　Ga-68-FAP-2286　but　with　a　prolonged　imaging　window　compared　to　Ga-68-FAP-2286.　In　acquired　drug-resistant　prostate　cancer　xenograft　nude　mice,　(AlF)-F-18-NOTA-FAP-2286　could　effectively　detect　tumor　lesions,　as　confirmed　by　immunohistochemical　analysis.　Conclusions:　(AlF)-F-18-NOTA-FAP-2286,　as　a　PSMA-independent　imaging　agent,　holds　promise　as　a　valuable　complementary　molecular　imaging　tool　for　assessing　acquired　resistance　to　PRLT.