Iranian Journal of Nuclear Medicine

Iranian Journal of Nuclear Medicine

Preclinical evaluation and dosimetric assessment of [177Lu]Lu FAP-2286 as a targeted therapy for FAP-expressing tumors

Articles in Press

Document Type : Original Article

Authors
Minoo Shakerian 1
Samaneh Zolghadri 2
Sedigheh Sina 1
Arezou Karimian 2
Hassan Yousefnia 2
1 Radiation Application Department, School of Mechanical Engineering, Shiraz University, Shiraz, Iran
2 Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran
10.22034/irjnm.2026.130444.1741
Abstract
Introduction: Fibroblast activation protein (FAP), predominantly expressed in the tumor microenvironment, represents a promising target for targeted radionuclide therapy (TRT). This study evaluates [177Lu]Lu-FAP-2286 as a FAP-targeted radiopharmaceutical for FAP-expressing tumors.
Methods: [177Lu]Lu-FAP-2286 was radiolabeled, and its radiochemical purity (RCP) was assessed by RTLC and HPLC. Stability was evaluated in PBS and human serum. Binding affinity, cellular internalization, and cytotoxicity were assessed in HEK FAP+ cells. Biodistribution was performed in normal and tumor-bearing mice. Organ absorbed doses were estimated by extrapolating murine biodistribution data using the MIRD formalism and OLINDA/EXM.
Results: RCP exceeded 99% under optimal conditions. The radiotracer exhibited high affinity for FAP+ cells (Kd = 0.45 nM) with >38% internalization at 6 h. MTT assays demonstrated significant cytotoxicity, reducing FAP+ cell viability to 16–38% at the highest concentration. Biodistribution revealed rapid blood clearance, marked tumor uptake, and low background activity. Dosimetric calculations identified the kidneys as the dose-limiting organ (0.27 mGy/MBq), with substantially lower doses to other organs.
Conclusion:  [177Lu]Lu-FAP-2286 demonstrated high RCP, strong FAP-binding affinity, favorable biodistribution with significant tumor uptake, and a promising dosimetric profile. These preliminary findings support further investigation of this radiopharmaceutical as a candidate for TRT of FAP-positive tumors; however, comprehensive in vivo therapeutic studies and subsequent clinical trials are warranted.
Keywords
Biodistribution studies
Preclinical evaluation
Dosimetry
FAP-2286
177Lu
Subjects
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Iranian Journal of Nuclear Medicine

Articles in Press, Accepted Manuscript
Available Online from 01 August 2026