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Integrin receptor αvβ3 and gastrin-releasing peptide receptor (GRPR) expression of tumors could be detected using PET imaging with radiolabeled Arg-Gly-Asp (RGD) and the antagonistic bombesin analog RM26, respectively. The purpose of this study was to investigate the dual receptor-targeting property of the heterodimer RGD-RM26-03 (denoted as LNC1015), demonstrate the tumor diagnostic value of [68Ga]Ga-LNC1015 in preclinical experiments, and evaluate its preliminary clinical feasibility. Methods: LNC1015 was designed and synthesized by linking cyclic RGD and the RM26 peptide. Preclinical pharmacokinetics were detected in a PC3 xenograft model using microPET and biodistribution studies. The clinical feasibility of [68Ga]Ga-LNC1015 PET/CT was performed in patients with breast cancer, and the results were compared with those of 18F-fluorodeoxyglucose (FDG). Results: [68Ga]Ga-LNC1015 had good stability in saline for at least 2 h, and favorable binding affinity and specificity were demonstrated in vitro and in vivo. The tumor uptake and retention of [68Ga]Ga-LNC1015 during PET imaging were improved compared with its monomeric counterparts [68Ga]Ga-RGD and [68Ga]Ga-RM26 at all the time points examined. In our initial clinical studies, the tumor uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in [68Ga]Ga-LNC1015 PET/CT were significantly higher than those in [18F]FDG PET/CT, resulting in high lesion detection rate and tumor delineation. Conclusion: The dual targeting radiotracer [68Ga]Ga-LNC1015 showed significantly improved tumor uptake and retention, as well as lower liver uptake than [68Ga]Ga-RGD and [68Ga]Ga-RM26 monomer. The first-in-human study showed high TBRs in patients, suggesting favorable pharmacokinetics and high clinical feasibility for PET/CT imaging of cancer. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the diagnostic performance and biodistribution of two similar PET agents, [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11, in the same group of primary prostate cancer (PCa) patients. Methods: Fifty patients with untreated, histologically confirmed PCa by needle biopsy were enrolled. Each patient underwent [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT within a week. In addition to visual analysis, the standardized uptake value (SUV) was measured for semiquantitative comparison and correlation analysis. Results: [68Ga]Ga-P16-093 PET/CT detected more positive tumors than [68Ga]Ga-PSMA-11 PET/CT (202 vs. 190, P = 0.002), both for intraprostatic lesions (48 vs. 41, P = 0.016) and metastatic lesions (154 vs. 149, P = 0.125), especially for intraprostatic lesions in low- and intermediate-risk PCa patients (21/23 vs. 15/23, P = 0.031). Furthermore, [68Ga]Ga-P16-093 PET/CT exhibited a significantly higher SUVmax for most matched tumors (13.7 ± 10.2 vs. 11.4 ± 8.3, P < 0.001). For normal organs, [68Ga]Ga-P16-093 PET/CT showed significantly lower activity in the kidney (SUVmean: 20.1 ± 6.1 vs. 29.3 ± 9.1, P < 0.001) and urinary bladder (SUVmean: 6.5 ± 7.1 vs. 20.9 ± 17.4, P < 0.001), but displayed a higher uptake in the parotid gland (SUVmean: 8.7 ± 2.6 vs. 7.6 ± 2.1, P < 0.001), liver (SUVmean: 7.0 ± 1.9 vs. 3.7 ± 1.3, P < 0.001), and spleen (SUVmean: 8.2 ± 3.0 vs. 5.2 ± 2.2, P < 0.001) than [68Ga]Ga-PSMA-11 PET/CT. Conclusion: [68Ga]Ga-P16-093 PET/CT demonstrated higher tumor uptake and better tumor detectability than [68Ga]Ga-PSMA-11 PET/CT, especially in low- and intermediate-risk PCa patients, which indicated that [68Ga]Ga-P16-093 may serve as an alternative agent for detection of PCa. Trial registration: 68Ga-P16-093 and 68Ga-PSMA-11 PET/CT Imaging in the Same Group of Primary Prostate Cancer Patients (NCT05324332, Registered 12 April 2022, retrospectively registered). URL of registry: https://clinicaltrials.gov/ct2/show/NCT05324332. [ABSTRACT FROM AUTHOR]

Background: Rosai–Dorfman disease (RDD) is a rare form of non-Langerhans cell histiocytic disease. The aim of this study was to review the characteristics of RDD using 18F-FDG PET/CT and determine its efficacy in the disease management. Results: A total of 28 RDD patients underwent 33 18F-FDG PET/CT scans for systematic assessment and follow-up. The common involved sites included the lymph nodes (17, 60.7%), upper respiratory tract (11, 39.3%), and skin (9, 32.1%). Five patients had more lesions detected in PET/CT images than in CT and/or MRI, including inapparent nodules (n = 5) and bone destruction (n = 3). After thorough treatment evaluation using PET/CT, the treatment strategies of 14 patients (14/16, 87.5%) were changed. Five patients underwent PET/CT twice during follow-up and the SUVs were significantly decreased (15.3 ± 3.4 vs. 4.4 ± 1.0, p = 0.02), which demonstrated disease improvement. Conclusions: 18F-FDG PET/CT contributed to displaying the holistic characteristics of RDD, in particular during initial assessment, treatment strategy adjustment, or efficacy evaluation, and could compensate for some disadvantages of CT and MRI images. [ABSTRACT FROM AUTHOR]

Background: Due to the temporal and spatial heterogeneity of human epidermal growth factor receptor 2 (HER2) expression in breast tumors, immunohistochemistry (IHC) cannot accurately reflect the HER2 status in real time, which may cause misguided treatment decisions. HER2-specific imaging can noninvasively determine HER2 status in primary and metastatic tumors. In this study, HER2 expression in breast cancer patients was determined in vivo by SPECT/CT of 99mTc-HP-Ark2, comparing with PET/CT of 18F-FDG lesion by lesion. Methods: A novel HER2-targeted peptide probe 99mTc-HP-Ark2 was constructed. Biodistribution and nanoScan SPECT/CT imaging were performed in mice models. The correlation between the quantified tumor uptake and HER2 expression in tumor cells was analyzed. In the pilot clinical study, a total of 34 breast cancer patients (mean age ± SD: 49 ± 10 y) suspected of having breast cancer according to mammography or ultrasonography were recruited at Peking Union Medical College Hospital, and 99mTc-HP-Ark2 SPECT/CT and 18F-FDG PET/CT were carried out with IHC and fluorescence in situ hybridization as validation. Results: Small animal SPECT/CT of 99mTc-HP-Ark2 clearly identified tumors with different HER2 expression. The quantified tumor uptake and tumor HER2 expression showed a significant linear correlation (r = 0.932, P < 0.01). Among the 36 primary lesions in the 34 patients, when IHC (2 +) or IHC (3 +) was used as the positive evaluation criterion, 99mTc-HP-Ark2 SPECT/CT imaging with a tumor-to-background ratio of 1.44 as the cutoff value reflected the HER2 status with sensitivity of 89.5% (17/19), specificity of 88.2% (15/17) and accuracy of 88.9% (32/36), while the 18F-FDG PET/CT showed sensitivity of 78.9% (15/19), specificity of 70.6% (12/17) and accuracy of 75.0% (27/36). In particular, 100% of IHC (3 +) tumors were all identified by 99mTc-HP-Ark2 SPECT/CT imaging. Conclusion: 99mTc-HP-Ark2 SPECT/CT can provide a specific, noninvasive evaluation of HER2 expression in breast cancer, showing great potential to guide HER2-targeted therapies in clinical practice. ClinicalTrials.gov Trial registration: NCT04267900. Registered 11th February 2020. Retrospectively registered, https://www.clinicaltrials.gov/ct2/results?pg=1&load=cart&id=NCT04267900. [ABSTRACT FROM AUTHOR]

Purpose: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging.[68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings.Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01).A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent.This study was registered on the ClinicalTrials.gov (NCT05937919).Methods: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging.[68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings.Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01).A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent.This study was registered on the ClinicalTrials.gov (NCT05937919).Results: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging.[68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings.Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01).A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent.This study was registered on the ClinicalTrials.gov (NCT05937919).Conclusion: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging.[68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings.Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01).A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent.This study was registered on the ClinicalTrials.gov (NCT05937919).Clinical trial registration: Claudin18.2 (CLDN18.2) is a novel target for diagnosis and therapy of gastrointestinal cancer. This study aimed to evaluate the safety and feasibility of a novel CLDN18.2-targeted nanobody, PMD22, labeled with gallium-68 ([68Ga]Ga), for detecting CLDN18.2 expression in patients with gastrointestinal cancer using PET/CT imaging.[68Ga]Ga-PMD22 was synthesized based on the nanobody, and its cell binding properties were assayed. Preclinical pharmacokinetics were determined in CLDN18.2-positive xenografts using microPET/CT. Effective dosimetry of [68Ga]Ga-PMD22 was evaluated in 5 gastrointestinal cancer patients, and PET/CT imaging of [68Ga]Ga-PMD22 and [18F]FDG were performed head-to-head in 16 gastrointestinal cancer patients. Pathological tissues were obtained for CLDN18.2 immunohistochemical (IHC) staining and comparative analysis with PET/CT findings.Cell binding assay showed that [68Ga]Ga-PMD22 had a higher binding ability to AGSCLDN18.2 and BGC823CLDN18.2 cells than to AGS and BGC823 cells (p < 0.001). MicroPET/CT images showed that [68Ga]Ga-PMD22 rapidly accumulated in AGSCLDN18.2 and BGC823CLDN18.2 tumors, and high contrast tumor to background imaging was clearly observed. In the pilot study, the effective dose of [68Ga]Ga-PMD22 was 1.68E-02 ± 1.45E-02 mSv/MBq, and the CLDN18.2 IHC staining result was highly correlated with the SUVmax/BKGstomach of [68Ga]Ga-PMD22 (rs = 0.848, p < 0.01).A novel [68Ga]Ga-labeled nanobody probe targeting CLDN18.2, [68Ga]Ga-PMD22, was established and preliminarily proved to be safe and effective in revealing CLDN18.2-positive gastrointestinal cancer, providing a basis for the clinical translation of the agent.This study was registered on the ClinicalTrials.gov (NCT05937919). [ABSTRACT FROM AUTHOR]