Work

Metastasis and angiogenesis: preclinical PET study on hepatocellular carcinoma (He/De) tumor models

Year: 2025

Type: article

Abstract: The use of animal models to study tumorigenesis and metastatic spread seems crucial to discover novel diagnostic and therapeutic targets that inhibit tumor development and progression. In this study a preclinical metastasis model of hepatocellular carcinoma (He/De) was established to explore metastases formation and related angiogenic processes using positron emission tomography (PET) and angiogenesis specific radiopharmaceuticals. Approximately 8±1 days after the subrenal capsule assay-based generation of the primary, secondary and tertiary transplanted metastatic He/De tumors in Fischer-344 rats, we used [ 18 F]FDG, [ 68 Ga]Ga-NOTA-c(NGR) and [ 68 Ga]Ga-NODAGA-[c(RGD)] 2 for the in vivo PET imaging of tumor development and angiogenesis. [ 18 F]FDG displayed the highest level of radioactivity among all investigated tracers. This pattern was consistent across all neoplastic lesions in each of the three transplantations. Comparing the two 68 Ga-labelled probes, the NGR compound showed significantly higher accumulation in the subrenally growing primary/secondary/tertiary He/De tumors (p≤0.05) and related parathymic lymph node metastases (PTLNs, p≤0.01 ) that could indicate higher expression level for aminopeptidase N/CD13 than for RGD-binding α v β 3 integrin. Progressive increase in the [ 18 F]FDG, [ 68 Ga]Ga-NOTA-c(NGR) and [ 68 Ga]Ga-NODAGA-[c(RGD)] 2 uptakes of both the subrenally growing He/De tumors and the PTLNs during the serial transplantations may imply increasing aggressivity. Overall, the currently developed experimental system provides a feasible platform for further investigation of metastatic spread.

Source: European Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ejps.2025.107211