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Purpose: This study aimed to evaluate the feasibility of using [68Ga]-fibroblast-activating protein inhibitor (FAPI) positron emission tomography (PET) imaging for diagnosing pulmonary fibrosis in a mouse model. We also examined its value in monitoring treatment response and compared it with traditional [18F]-fluorodeoxyglucose (FDG) PET and computed tomography (CT) imaging. Methods: A model of idiopathic pulmonary fibrosis was established using intratracheal injection of bleomycin (BLM, 2 mg/kg) into C57BL/6 male mice. For the treatment of IPF, a daily oral dose of 400 mg/kg/day of pirfenidone was administered from 9 to 28 days after the establishment of the model. Disease progression and treatment efficacy were assessed at different stages of the disease every week for four weeks using CT, [18F]FDG PET, and [68Ga]FAPI PET (baseline imaging performed at week 0). Mice were sacrificed and lung tissues were harvested for hematoxylin-eosin staining, picrosirius red staining, and immunohistochemical staining for glucose transporter 1 (GLUT1) and FAP. Expression levels of GLUT1 and FAP in pathological sections were quantified. Correlations between imaging parameters and pathological quantitative values were analyzed. Results: CT, [18F]FDG PET and [68Ga]FAPI PET revealed anatomical and functional changes in the lung that reflected progression of pulmonary fibrosis. In untreated mice with pulmonary fibrosis, lung uptake of [18F]FDG peaked on day 14, while [68Ga]FAPI uptake and mean lung density peaked on day 21. In mice treated with pirfenidone, mean lung density and lung uptake of both PET tracers decreased. Mean lung density, [18F]FDG uptake, and [68Ga]FAPI uptake correlated well with quantitative values of picrosirius red staining, GLUT1 expression, and FAP expression, respectively. Conclusions: Although traditional CT and [18F]FDG PET reflect anatomical and metabolic status in fibrotic lung, [68Ga]FAPI PET provides a means of evaluating fibrosis progression and monitoring treatment response. [ABSTRACT FROM AUTHOR]

Purpose: Intracytoplasmic melanin pigment is a characteristic of clear cell sarcoma (CCS), which is a particularly deadly type of soft-tissue sarcoma. [18F]-N-(2-(diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)picolinamide ([18F]-PFPN) is a positron emission tomography (PET) probe characterized by high melanin affinity. Therefore, this study aimed to investigate the feasibility of melanin-targeted [18F]-PFPN PET in patients with CCS. Methods: This prospective single-centre study recruited patients with pathologically confirmed CCS. [18F]-FDG PET/computed tomography and [18F]-PFPN PET/magnetic resonance imaging scans were performed within 1 week of each other. The lesion numbers and [18F]-FDG and [18F]-PFPN PET parameters (maximum standardized uptake value [SUVmax], mean standardized uptake value [SUVmean], metabolic/melanotic tumour volume [MTV/MLTV], and total lesion glycolysis/melanin [TLG/TLM]) were collected. Results: Three patients with CCS were recruited and received PET imaging. A total of 56 lesions were detected on [18F]-PFPN PET, including primary tumour and distant metastases. Identical lesions were not detected on [18F]-PFPN and [18F]-FDG PET. Twelve lesions (12/39, 30.77%) on [18F]-FDG imaging were missed on [18F]-PFPN, and 20 lesions (20/47, 42.55%) on [18F]-PFPN imaging were missed on [18F]-FDG. In quantitative analysis, the [18F]-FDG SUVmean (4.60 ± 3.24) was higher than the [18F]-PFPN SUVmean (3.0 ± 2.63) in all lesions (P = 0.01). No significant correlations were found between the SUVmax, SUVmean, MLTV/MTV, and TLM/TLG values of [18F]-PFPN and [18F]-FDG (P > 0.05). Conclusion: Melanin-targeted [18F]-PFPN PET imaging is feasible for the diagnosis of CCS. Different imaging features were displayed on [18F]-PFPN and [18F]-FDG PET imaging, demonstrating the complementary role of the tracers. Combined use of the two imaging modalities would be preferred in patients with CCS. Clinical Trial Registration: NCT05963035. [ABSTRACT FROM AUTHOR]

Purpose: The integrin αvβ3 and aminopeptidase N (APN/CD13) play vital roles in the tumor angiogenesis process. They are highly expressed in a variety of tumor cells and proliferating endothelial cells during angiogenesis, which have been considered as highly promising targets for tumor imaging. Arginine-glycine-aspartic (RGD) and asparagine-glycine-arginine (NGR) are two peptides specifically binding to the integrin αvβ3 and CD13, respectively. In this study, we optimized our previously developed probe and preclinically evaluated the new integrin αvβ3 and CD13 dual-targeted probe, NOTA-RGD-NGR (denoted as HX01) radiolabeled with 68Ga, in 10 different subcutaneous and orthotopic tumor models. Methods: The specific activity and radiochemical purity of [68Ga]Ga-HX01 were identified. The dual-receptor targeting ability was confirmed by a series of blocking studies and partly muted tracers using BxPC-3 xenograft model. The dynamic imaging study and dose escalation study were explored to determine the optimal imaging time point and dosage in the BxPC-3 xenograft model. Next, we established a variety of subcutaneous and orthotopic tumor models including pancreas (BxPC-3), breast (MCF-7), gallbladder (NOZ), lung (HCC827), ovary (SK-OV-3), colorectal (HCT-8), liver (HuH-7), stomach (NUGC-4), and glioma (U87) cancers. All models underwent [68Ga]Ga-HX01 PET/CT imaging about 2 weeks post-inoculation, with a subset of them undergoing [18F]FDG PET/CT scan performed concurrently, and their results were compared. In addition, ex vivo biodistribution studies were also performed for verifying the semi-quantitative results of the non-invasive PET images. Results: [68Ga]Ga-HX01 significantly outperformed single target probes in the BxPC-3 xenograft model. All blocking and single target groups exhibited significantly descending tumor uptake. The high tumor uptakes were found in BxPC-3, MCF-7, and NOZ subcutaneous tumors (%ID/g > 1.1), while middle uptakes were observed in HCC827, SK-OV-3, HCT-8, and HuH-7 subcutaneous tumor (%ID/g 0.7–1.0). Due to the low background, the tumor-to-muscle and tumor-to-blood ratios of [68Ga]Ga-HX01 were higher than that of [18F]FDG. Conclusions: [68Ga]Ga-HX01, as a dual target imaging agent, exhibited superior in vivo performance in different subcutaneous and orthotopic mice models of human tumors over [18F]FDG and its respectively mono-receptor targeted agents, which warrants the future clinical translation for tumor imaging. [ABSTRACT FROM AUTHOR]

Purpose: Positron emission tomography (PET) using [18F]-PFPN, a melanin-targeted imaging tracer, has excellent diagnostic performance in patients with melanoma. This study aimed to investigate its value in prognostication and determine predictors of progression-free survival (PFS) and overall survival (OS). Methods: We reviewed melanoma patients who underwent [18F]-PFPN and [18F]-FDG PET from February 2021 to July 2022. Clinical characteristics, follow-up data, and the following [18F]-PFPN PET parameters were recorded: maximum standardized uptake value (SUVmax), whole-body melanotic tumoral volume (WBMTV), and whole-body total lesion melanin (WBTLM). Receiver operating characteristic (ROC), Kaplan–Meier and Cox regression analyses were performed. Results: Seventy-six patients (47 men and 29 women; mean age, 57.99 ± 10.72 years) were included for analysis. Median follow-up was 12.0 months (range: 1–22 months). Eighteen patients died and 38 experienced progression. Median OS was 17.60 months (95% confidence interval, 15.89–19.31). In the ROC analysis, [18F]-PFPN PET parameters were superior to those of [18F]-FDG PET in prognosticating death and disease progression. PFS and OS were significantly better in patients with lower SUVmax, WBMTV, and WBTLM on [18F]-PFPN PET (log-rank, P < 0.05). In the univariate analyses, distant metastasis, SUVmax, WBMTV, and WBTLM were significantly associated with cumulative incidence of PFS and OS (P < 0.05). In the multivariate analysis, SUVmax was an independent predictor of PFS and OS. Conclusions: [18F]-PFPN PET has a role in prognostication of melanoma patients. Patients with higher [18F]-PFPN SUVmax have worse prognosis. Clinical Trial Registration: ClinicalTrials.gov, NCT05645484. Registered 9 December, 2022, https://clinicaltrials.gov/ct2/show/NCT05645484?cond=The+Prognostic+Value+of+18F-PFPN+PET+Imaging+in+Patients+With+Malignant+Melanoma&draw=2&rank=1 [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the feasibility of using [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 and [177Lu]Lu-Evans blue (EB)-PSMA-617 for in vivo radioligand therapy by single-dose administration in a PSMA-positive hepatocellular carcinoma (HCC) xenograft mouse model. Methods: [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 were prepared, and labelling efficiency and radiochemical purity were determined. A HepG2 human HCC subcutaneous xenograft mouse model was established. After intravenous injection of [177Lu]Lu-PSMA-617 or [177Lu]Lu-EB-PSMA-617 (37 MBq) into the mouse model, single-photon emission computed tomography/computed tomography (SPECT/CT) was performed. Biodistribution studies were conducted to verify targeting specificity and pharmacokinetics. In the radioligand therapy study, mice were randomized into 4 groups: 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, 7.4 MBq [177Lu]Lu-EB-PSMA-617, and saline (control). A single-dose administration was applied at the beginning of therapy studies. Tumor volume, body weight, and survival were monitored every 2 days. After the end of therapy, mice were euthanized. Tumors were then weighed, and systemic toxicity was evaluated via blood testing and histological examination of healthy organs. Results: [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 were successfully prepared with high purity and stability. SPECT/CT and biodistribution showed that tumor uptake was higher and persisted longer for [177Lu]Lu-EB-PSMA-617 compared with [177Lu]Lu-PSMA-617. [177Lu]Lu-PSMA-617 was rapidly cleared from the blood, while [177Lu]Lu-EB-PSMA-617 persisted for significantly longer. In radioligand therapy studies, tumor growth was significantly suppressed in the 37 MBq [177Lu]Lu-PSMA-617, 18.5 MBq [177Lu]Lu-PSMA-617, and 7.4 MBq [177Lu]Lu-EB-PSMA-617 groups compared to the saline group. Median survival was 40, 44, 43, and 30 days, respectively. No healthy organ toxicity was observed in safety and tolerability evaluation. Conclusions: Radioligand therapy using [177Lu]Lu-PSMA-617 and [177Lu]Lu-EB-PSMA-617 significantly suppressed tumor growth and prolonged survival time in PSMA-positive HCC xenograft mice without obvious toxicity. These radioligands appear promising for clinical use in humans, and future studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to determine whether Q.Clear positron emission tomography (PET) reconstruction may reduce tracer injection dose or shorten scanning time in 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI) PET/magnetic resonance (MR) imaging. Methods: We retrospectively collected cases of 68 Ga-FAPI whole-body imaging performed on integrated PET/MR. PET images were reconstructed using three different methods: ordered subset expectation maximization (OSEM) reconstruction with full scanning time, OSEM reconstruction with half scanning time, and Q.Clear reconstruction with half scanning time. We then measured standardized uptake values (SUVs) within and around lesions, alongside their volumes. We also evaluated image quality using lesion-to-background (L/B) ratio and signal-to-noise ratio (SNR). We then compared these metrics across the three reconstruction techniques using statistical methods. Results: Q.Clear reconstruction significantly increased SUVmax and SUVmean within lesions (more than 30%) and reduced their volumes in comparison with OSEM reconstruction. Background SUVmax also increased significantly, while background SUVmean showed no difference. Average L/B values for Q.Clear reconstruction were only marginally higher than those from OSME reconstruction with half-time. SNR decreased significantly in Q.Clear reconstruction compared with OSEM reconstruction with full time (but not half time). Differences between Q.Clear and OSEM reconstructions in SUVmax and SUVmean values within lesions were significantly correlated with SUVs within lesions. Conclusions: Q.Clear reconstruction was useful for reducing PET injection dose or scanning time while maintaining the image quality. Q.Clear may affect PET quantification, and it is necessary to establish diagnostic recommendations based on Q.Clear results for Q.Clear application. [ABSTRACT FROM AUTHOR]