[¹⁷⁷Lu]Lu-PSMA^I&T is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged. A major finding was a correlation between the specific activity and the formation of a pre-peak, presumably caused by radiolysis. Hence, nonradioactive reference standards were irradiated with an X-ray source and the formed pre-peak was subsequently identified as a deiodination product by UPLC-MS. To confirm the occurrence of the same deiodinated side product in the routine batch, a customized deiodinated precursor was radiolabeled and analyzed with the same HPLC setup, revealing an identical retention time to the pre-peak in the formerly synthesized routine batches. Additionally, further cyclization products of [¹⁷⁷Lu]Lu-PSMA^I&T were identified as major contributors to radiochemical impurities. The comparison of two HPLC methods showed the likelihood of the overestimation of the radiochemical purity during the synthesis of [¹⁷⁷Lu]Lu-PSMA^I&T. Finally, a prospective cost reduction through an optimization of the production process was shown.

Background/Objectives: Fibroblast activation protein (FAP) has gained tremendous traction as a target for tumor imaging and cancer treatment, while also playing a key role in fibrosis. Our study aimed to evaluate [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for PET imaging of replacement fibrosis following myocardial infarction (MI) or interstitial fibrosis associated with hypertrophy. Methods: MI or transverse aortic constriction (TAC)-induced hypertrophy was induced in C57BL/6 mice, with sham-operated animals serving as controls. At multiple time points during disease progression (1, 2, and 6 weeks post-surgery), [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans were performed, followed by ex vivo investigations. Additionally, in vitro cell uptake experiments simulating hypertrophy were conducted. Results: Cardiac uptake of [⁶⁸Ga]Ga-DATA5m.SA.FAPi significantly increased two weeks after MI induction (MI: 2.1 ± 0.2%ID/g, n = 7 vs. SHAM: 1.1 ± 0.2%ID/g, n = 5; p = 0.002), confirmed by ex vivo autoradiography. No significant difference was observed at six weeks post-MI (MI: 1.1 ± 0.1%ID/g, n = 4 vs. SHAM: 0.8 ± 0.0%ID/g, n = 3), indicating infarct healing completion. In contrast, TAC mice showed increased uptake after six weeks (TAC: 1.8 ± 0.2%ID/g, n = 6; p = 0.007), related to interstitial fibrosis progression. Consistently, high-stretched cardiac fibroblasts demonstrated a higher uptake compared to low-stretched conditioned ones, suggesting the stretch mediates regulation of FAP. Conclusions: This study demonstrated the efficacy of [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for longitudinal imaging of cardiac fibrosis in response to different cardiac injuries. In vivo FAP imaging during cardiac remodeling may serve as a valuable tool for diagnosing and predicting disease progression, ultimately aiding in the clinical management of patients.

Background/Objectives: Radiolabeled fibroblast activation protein inhibitors (FAPIs) are emerging as promising imaging agents assessing fibrotic diseases. This study evaluates [⁶⁸Ga]Ga-DATA^5m.SA.FAPi for imaging pulmonary fibrosis in two mouse models, bleomycin-induced (BLM) and a transgenic (fra-2^tg) model, both displaying characteristics of human pulmonary fibrotic diseases. Methods: In the BLM model, C57BL/6 mice were treated with bleomycin or isotonic sodium chloride (controls) for 4, 5, and 6 weeks, followed by [⁶⁸Ga]Ga-DATA^5m.SA.FAPi PET/CT scans. Fra-2^tg mice and wildtype (WT) littermates underwent at 7, 11, and 18/19 weeks of age a PET/CT scan. The selected timepoints correspond to early, middle, and late disease stages for each model. Imaging was complemented by ex vivo quantification, histological, and immunohistochemical (IHC) analyses. Results: In BLM mice, pulmonary [⁶⁸Ga]Ga-DATA^5m.SA.FAPi uptake showed a trend toward increase as early as 5 weeks of treatment compared with the controls, which was confirmed by ex vivo analysis (BLM: 3.31 ± 0.29%ID/g, n = 5; control: 1.61 ± 0.29%ID/g, n = 4; p = 0.0035). In fra-2^tg mice, no significant differences could be detected. IHC revealed elevated pulmonary FAP expression specifically at early (BLM) and mild (fra-2^tg) disease stages, whereas for BLM, tracer uptake was more pronounced at later stages. Conclusions: Our findings complement and extend observations from previous studies and support the potential of FAPI tracers as molecular imaging agents for pulmonary fibrosis.