The overexpression of fibroblast activation protein-α (FAP) in solid cancers relative to levels in normal tissues has led to its recognition as a target for delivering agents directly to tumors. Radiolabeled quinoline-based FAP ligands have established clinical feasibility for tumor imaging, but their therapeutic potential is limited due to suboptimal tumor retention, which has prompted the search for alternative pharmacophores. One such pharmacophore is the boronic acid derivative N-(pyridine-4-carbonyl)-d-Ala-boroPro, a potent and selective FAP inhibitor (FAPI). In this study, the diagnostic and therapeutic (theranostic) potential of N-(pyridine-4-carbonyl)-d-Ala-boroPro–based metal-chelating DOTA-FAPIs was evaluated. Methods: Three DOTA-FAPIs, PNT6555, PNT6952, and PNT6522, were synthesized and characterized with respect to potency and selectivity toward soluble and cell membrane FAP; cellular uptake of the Lu-chelated analogs; biodistribution and pharmacokinetics in mice xenografted with human embryonic kidney cell–derived tumors expressing mouse FAP; the diagnostic potential of ⁶⁸Ga-chelated DOTA-FAPIs by direct organ assay and small-animal PET; the antitumor activity of ¹⁷⁷Lu-, ²²⁵Ac-, or ¹⁶¹Tb-chelated analogs using human embryonic kidney cell–derived tumors expressing mouse FAP; and the tumor-selective delivery of ¹⁷⁷Lu-chelated DOTA-FAPIs via direct organ assay and SPECT. Results: DOTA-FAPIs and their ^natGa and ^natLu chelates exhibited potent inhibition of human and mouse sources of FAP and greatly reduced activity toward closely related prolyl endopeptidase and dipeptidyl peptidase 4. ⁶⁸Ga-PNT6555 and ⁶⁸Ga-PNT6952 showed rapid renal clearance and continuous accumulation in tumors, resulting in tumor-selective exposure at 60 min after administration. ¹⁷⁷Lu-PNT6555 was distinguished from ¹⁷⁷Lu-PNT6952 and ¹⁷⁷Lu-PNT6522 by significantly higher tumor accumulation over 168 h. In therapeutic studies, all 3 ¹⁷⁷Lu-DOTA-FAPIs exhibited significant antitumor activity at well-tolerated doses, with ¹⁷⁷Lu-PNT6555 producing the greatest tumor growth delay and animal survival. ²²⁵Ac-PNT6555 and ¹⁶¹Tb-PNT6555 were similarly efficacious, producing 80% and 100% survival at optimal doses, respectively. Conclusion: PNT6555 has potential for clinical translation as a theranostic agent in FAP-positive cancer.