Biodistribution Assessment of a Novel 68Ga-Labeled Radiopharmaceutical in a Cancer Overexpressing CCK2R Mouse Model: Conventional and Radiomics Methods for Analysis.

The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

Glypican-3 and Hep Par-1 are Useful Biomarkers in the Cytologic Assessment of Ascites.

Till date, the utility of cytologic assessment of ascites for the identification of hepatocellular carcinoma (HCC) cells is still debated and the usefulness of immunocytochemistry for glypican-3 (GPC3) and Hep Par-1 in this setting has not been reported. Liquid-based cytology of ascitic fluid of 28 cirrhotic patients was performed and the spots obtained were stained with hematoxylin and eosin, papanicolau, and with GPC3 and Hep Par-1 antibodies. GPC3 and Hep Par-1 antibodies stained positively the atypical cells in the ascites of 2 patients with HCC showing an exophytic growth pattern. The specimens of the patients with nonexophytic HCC, other non-HCC cancers, or cirrhosis stained negatively. We hypothesize a relationship with the exophytic growth of the tumor. Thus, GPC3 and Hep Par-1 are useful in the cytologic assessment of peritoneal effusions to distinguish mesothelial cells and neoplastic non-HCC cells from HCC cells, presence of which, however, represent a very rare event. This is the first study in which GPC3 and Hep Par-1 immunostaining has been used in the cytologic assessment of HCC ascites.