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

Barkóczi, Alexandra and Képes, Zita and Péliné Szabó, Judit and Dienes, Renáta Adél and Károlyi, Péter Kálmán and Papp, Tamás and Kálmán-Szabó, Ibolya and Sass, Tamás and Opposits, Gábor and Kertész, István and Hajdu, István and Trencsényi, György and Deák, Ádám (2025) Metastasis and angiogenesis: preclinical PET study on hepatocellular carcinoma (He/De) tumor models. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 212. No. 107211. ISSN 0928-0987

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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 [ 18F]FDG, [ 68Ga]GaNOTA-c(NGR) and [ 68Ga]Ga-NODAGA-[c(RGD)]2 for the in vivo PET imaging of tumor development and angiogenesis. [ 18F]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 68Ga-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 αvβ3 integrin. Progressive increase in the [ 18F]FDG, [ 68Ga]Ga-NOTA-c(NGR) and [ 68Ga]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.

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