Pharmacokinetic Evaluation of Fibroblast Activation Protein-Targeted Radiopharmaceutical Uptake in Low-Stage Rectal Cancer Tumor Microenvironment.

Authors

XuDong Zhang, Ke Duan, YuHan Long, Tong Zhou

Published in

Cancer biotherapy & radiopharmaceuticals. Pages 10849785261479557. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Purpose: Radionuclide therapy targeting fibroblast activation protein (FAP) offers an effective treatment for tumors with high FAP expression, such as those imaged with ⁶⁸Ga-fibroblast activation protein inhibitor (FAPI) and treated with ¹⁷⁷Lu-FAPI. Personalized therapy planning, based on imaging-derived standardized uptake values, pharmacokinetic parameters, and dosimetric modeling, is essential to optimize therapeutic outcomes while minimizing toxicity to healthy tissues.Methods and Results: The study develops a comprehensive personalized therapy planning framework integrating ⁶⁸Ga-FAPI positron emission tomography (PET), pharmacokinetic modeling, and voxel-based dosimetry for optimized tumor doses and safety in ¹⁷⁷Lu-FAPI radionuclide therapy. A cohort of 26 patients (mean age: 56.3 ± 9.2 years) with stage I-II rectal cancer underwent ⁶⁸Ga-FAPI PET/computed tomography imaging after intravenous injection of ⁶⁸Ga-FAPI (150-250 MBq). SUV_max ranged from 8.5 to 12.5, with imaging performed at multiple time points (10, 30, 60, and 120 min) to capture tracer kinetics. Pharmacokinetic modeling was used to estimate uptake rate (K₁ = 0.182 ± 0.036 min^-1), washout rate (k₂ = 0.094 ± 0.021 min^-1), and retention coefficient (k₃ = 0.138 ± 0.028 min^-1).Results: Voxel-based dosimetry derived absorbed doses using time-activity curves and radionuclide-specific S-values. Activity scaling was applied to estimate tumor doses with 3-7 GBq of ¹⁷⁷Lu-FAPI. With 5-7 GBq of ¹⁷⁷Lu-FAPI, 92.3% of patients received tumor doses of at least 20 Gy, ranging from 18.2 to 26.4 Gy. Kidney dosages ranged from 2.2 to 5.0 Gy, whereas liver doses varied from 1.7 to 4.1 Gy. SUV_max showed a high correlation with absorbed dose (r = 0.88, p < 0.001).Conclusions: The methodology successfully enhanced tumor dose coverage while ensuring organ safety through activity optimization. This system offers a clinically applicable approach to targeted radionuclide therapy by combining PET imaging, pharmacokinetics, and dosimetry to deliver optimal tumor doses while meeting organ-at-risk constraints.

PMID:
42629967
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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