J Cancer 2017; 8(5):774-785. doi:10.7150/jca.17550

Research Paper

In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA)

István Kertész1*, András Vida2,3*, Gábor Nagy4, Miklós Emri1, Antal Farkas5, Adrienn Kis1, János Angyal6, Noémi Dénes1, Judit P. Szabó1, Tünde Kovács2,3, Péter Bai2,3,7, György Trencsényi1,4✉

1. Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary;
2. Department of Medical Chemisty, University of Debrecen, Debrecen, Hungary;
3. MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, Hungary;
4. Scanomed LTD, Debrecen, Hungary;
5. Department of Urology, University of Debrecen, Debrecen, Hungary;
6. Department of Periodontology, University of Debrecen, Debrecen, Hungary;
7. Research Center for Molecular Medicine, University of Debrecen, Hungary.
*Equal contribution.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Kertész I, Vida A, Nagy G, Emri M, Farkas A, Kis A, Angyal J, Dénes N, Szabó JP, Kovács T, Bai P, Trencsényi G. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA). J Cancer 2017; 8(5):774-785. doi:10.7150/jca.17550. Available from http://www.jcancer.org/v08p0774.htm

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Purpose: The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques.

Methods: Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (68Ga-NODAGA-PCA). The melanin specificity of 68Ga-NODAGA-PCA was tested in vitro, ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68Ga-NODAGA-PCA and 18FDG tracers.

Results: 68Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%<), at all cases. In vitro experiments showed that 68Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher 68Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18FDG and 68Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly (p≤0.05 and p≤0.01) higher using 68Ga-NODAGA-PCA than the 18FDG accumulation.

Conclusion: Our novel radiotracer 68Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo.

Keywords: B16-F10 tumor, 18FDG, 68Ga-NODAGA-PCA, Melanoma malignum, Positron Emission Tomography, Procainamide.