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Aim: Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis, presenting the most aggressive form of interstitial lung diseases (ILDs). Activated fibroblasts are crucial for pathological processes. Fibroblast activation protein (FAP) inhibitor (FAPI) tracers would be promising imaging agents for these diseases. The purpose of this study was to evaluate a 99mTc-labeled FAPI tracer, 99mTc-HFAPI imaging in IPF patients. Methods: Eleven IPF patients (nine males and two females; age range 55–75 year) were included in this pilot study. 99mTc-HFAPI serial whole-body scintigraphy at 5 min, 20 min, 40 min, 1 h, 2 h, 3 h, 4 h, and 6 h was acquired for dynamic biodistribution and dosimetry estimation in seven representative patients. SPECT/CT tomography fusion imaging of the chest region was performed in all patients at 4 h post-injection, which was considered as the optimal acquisition time. Dosimetry was calculated using OLINDA/EXM software (version 2.0; HERMES Medical Solutions). The quantified or semi-quantified standardized uptake values (SUVs) and lesion-to-background ratios (LBRs) of affected lung parenchyma were also calculated. The high-resolution CT (HRCT) stage was determined with visual evaluation, and the total HRCT score of each patient was measured using a weighting factor formula. Pulmonary function tests (PFTs) were recorded as well. Then, the relationships between the 99mTc-HFAPI results, disease extent on HRCT, and PFT results were investigated. Results: Normal physiological uptake of 99mTc-HFAPI was observed mainly in the liver, intestinal tract, pancreas, gallbladder, and to a lesser extent in the spleen, kidneys, and thyroid, with no apparent retention in the blood circulation at the late time point. The mean injected activity of 99mTc-HFAPI was 813.4 MBq (range 695.6–888.0 MBq). No subjective side effects were noticed. The average whole-body effective dose was 0.0041 mSv/MBq per patient. IPF patients exhibited elevated pulmonary 99mTc-HFAPI uptake in abnormal lung regions, which was correlated with fibrotic regions on HRCT. Among different HRCT stage groups, both SUVmax and LBR showed significant differences (p < 0.001). The higher HRCT stage demonstrated significantly higher SUVmax and LBR. A linear correlation between 99mTc-HFAPI uptake and total HRCT score was observed for SUVmax (r = 0.7839, F = 54.41, p = 0.0094) and LBR (r = 0.7402, F = 56.33, p = 0.0092). 99mTc-HFAPI uptake also had moderate correlations with PFT results. Conclusions: Our preliminary data show that the 99mTc-HFAPI SPECT imaging is a promising new imaging modality in IPF patients. Investigations of its clinical value in monitoring disease progression and treatment response are needed in the future.

Clinical trials have shown the significant efficacy of [177Lu]Lu-PSMA-617 for treating prostate cancer. However, the pharmacokinetic characteristics and therapeutic performance of [177Lu]Lu-PSMA-617 still need further improvement to meet clinical expectations. The aim of this study was to evaluate the feasibility and therapeutic potential of three novel 177Lu-labeled ligands for the treatment of prostate cancer. The novel ligands were efficiently synthesized and radiolabeled with non-carrier added 177Lu; the radiochemical purity of the final products was determined by Radio-HPLC. The specific cell-binding affinity to PSMA was evaluated in vitro using prostate cancer cell lines 22Rv1and PC-3. Blood pharmacokinetic analysis, biodistribution experiments, small animal SPCET imaging and treatment experiments were performed on normal and tumor-bearing mice. Among all the novel ligands developed in this study, [177Lu]Lu-PSMA-Q showed the highest uptake in 22Rv1 cells, while there was almost no uptake in PC-3 cells. As the SPECT imaging tracer, [177Lu]Lu-PSMA-Q is highly specific in delineating PSMA-positive tumors, with a shorter clearance half-life and higher tumor-to-background ratio than [177Lu]Lu-PSMA-617. Biodistribution studies verified the SPECT imaging results. Furthermore, [177Lu]Lu-PSMA-Q serves well as an effective therapeutic ligand to suppress tumor growth and improve the survival rate of tumor-bearing mice. All the results strongly demonstrate that [177Lu]Lu-PSMA-Q is a PSMA-specific ligand with significant anti-tumor effect in preclinical models, and further clinical evaluation is worth conducting.

Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have become some of the most promising tools for the diagnosis and therapy prostate cancer (PCa). The structure of existing PSMA-targeted PET tracers still needs to be optimized to improve their pharmacokinetic properties and tumor-to-background ratio. In this study, we modified the structure of a well-studied PSMA tracer, and six novel tracers with variable hydrophilicity and pharmacokinetics were developed and evaluated both in vitro and in vivo. All of the novel tracers showed high hydrophilicity (log p = −2.99 ± 0.33 to −3.49 ± 0.01), rapid clearance rates (elimination half-times = 15.55 to 35.97 min), and high affinity for PSMA (Ki = 8.11 ± 0.49 to 42.40 ± 2.11 nM) in vitro. Specific cell binding and micro-PET experiments showed that [68Ga]Ga-PSMA-Q displayed the highest specific PSMA+ cell uptake (3.75 ± 0.35 IA%/106 at 60 min), tumor uptake (SUVmax = 0.97 ± 0.24 at 60 min p.i.), and tumor-to-muscle ratio (59.33 ± 5.72 at 60 min p.i.), while the tumor-to-muscle ratio was much higher than that of [68Ga]Ga-PSMA-617. The results of this study validate the clinical potential of [68Ga]Ga-PSMA-Q for PET imaging and further targeted therapy of prostate cancer.