Molecular SPECT/CT Profiling of Claudin18.2 Expression In Vivo: Implication for Patients with Gastric Cancer.

Zolbetuximab (IMAB362), a monoclonal antibody targeting Claudin18.2 (CLDN 18.2), demonstrates a significant clinical benefit in patients with advanced gastroesophageal cancers. The noninvasive assessment of CLDN18.2 expression through molecular imaging offers a potential avenue for expedited monitoring and the stratification of patients into risk groups. This study elucidates that CLDN18.2 is expressed at a noteworthy frequency in primary gastric cancers and their metastases. The iodogen method was employed to label IMAB362 with 123I/131I. The results demonstrated the efficient and reproducible synthesis of 123I-IMAB362, with a specific binding affinity to CLDN18.2. Immuno-single-photon emission computed tomography (SPECT) imaging revealed the rapid accumulation of 123I-IMAB362 in gastric cancer xenografts at 12 h, remaining stable for 3 days in patient-derived tumor xenograft models. Additionally, tracer uptake of 123I-IMAB362 in MKN45 cells surpassed that in MKN28 cells at each time point, with tumor uptake correlating significantly with CLDN18.2 expression levels. Positron emission tomography/computed tomography imaging indicated that tumor uptake of 18F-FDG and the functional/viable tumor volume in the 131I-IMAB362 group were significantly lower than those in the 123I-IMAB362 group on day 7. In conclusion, 123I-IMAB362 immuno-SPECT imaging offers an effective method for direct, noninvasive, and whole-body quantitative assessment of tumor CLDN18.2 expression in vivo. This approach holds promise for accelerating the monitoring and stratification of patients with gastric cancer.

A Novel Risk Score Model for the Differential Diagnosis of Type 2 Diabetic Nephropathy: A Multicenter Study.

Introduction: DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment. Methods: A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients "ß" to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves. Results: Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml/min/1.73 m2, 24 h UTP ≥ 3 g, and no hematuria were independent risk factors (P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively. Conclusion: The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Idarubicin-loaded biodegradable microspheres enhance sensitivity to anti-PD1 immunotherapy in transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary hepatocellular carcinoma (HCC). However, conventional TACE formulations such as epirubicin-lipiodol emulsion are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. To overcome these limitations, we used biodegradable Idarubicin loaded microspheres (BILMs), which were prepared from gelatin and carrageenan and could be loaded with Idarubicin (IDA-MS). The morphology and the ability to load and release IDA of BILMs were characterized in vitro. We evaluated tumor changes and side effects after TACE treatment with IDA-MS in VX2 rabbit and C57BL/6 mice HCC models. In addition, the effect of IDA-MS on the tumor immune microenvironment of HCC tumors was elucidated via mass spectrometry and immunohistochemistry. Result showed that IDA-MS was developed as a new TACE formulation to overcome the poor delivery of drugs due to rapid elimination of the anticancer drug into the systemic circulation. We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment. STATEMENT OF SIGNIFICANCE: Conventional transarterial chemoembolization (TACE) formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in hepatocellular carcinoma (HCC). To overcome these limitations, we used biodegradable microspheres called BILMs, which could be loaded with Idarubicin (IDA-MS). We demonstrated in rabbits and mice HCC models that TACE with IDA-MS resulted in significant tumor shrinkage and no more severe adverse events than those observed in the IDA group. TACE with IDA-MS could also significantly enhance the sensitivity of anti-PD1 immunotherapy, improve the expression of CD8+ T cells, and activate the tumor immune microenvironment in HCC. This study provides a new approach for TACE therapy and immunotherapy and illuminates the future of HCC treatment.