title: In VivoImaging of Experimental Melanoma Tumors using the Novel Radiotracer68Ga-NODAGA-Procainamide (PCA).
abstract: OBJECTIVE
  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 novel68Ga-labeled NODAGA-PCA moleculein vitroandin vivousing PET techniques.
  
  
  METHODS
  Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 (68Ga-NODAGA-PCA). The melanin specificity of68Ga-NODAGA-PCA was testedin vitro,ex vivoandin vivousing 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 for68Ga-NODAGA-PCA and18FDG 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 vitroexperiments showed that68Ga-NODAGA-PCA uptake of B16-F10 cells was significantly (p≤0.01) higher than Melur cells.Ex vivobiodistribution andin vivoPET/CT studies using subcutaneous and metastatic tumor models showed significantly (p≤0.01) higher68Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where18FDG and68Ga-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 andp≤0.01) higher using68Ga-NODAGA-PCA than the18FDG accumulation.
  
  
  CONCLUSIONS
  Our novel radiotracer68Ga-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 metastasesin vivo.
authors.affiliation: Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Kertész
authors.affiliation: Department of Medical Chemisty, University of Debrecen, Debrecen, Hungary;; MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Vida
authors.affiliation: Scanomed LTD, Debrecen, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Nagy
authors.affiliation: Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Emri
authors.affiliation: Department of Urology, University of Debrecen, Debrecen, Hungary.
authors.forename: Antal
authors.initials: A
authors.lastname: Farkas
authors.affiliation: Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Adrienn
authors.initials: A
authors.lastname: Kis
authors.affiliation: Department of Periodontology, University of Debrecen, Debrecen, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Angyal
authors.affiliation: Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Noémi
authors.initials: N
authors.lastname: Dénes
authors.affiliation: Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: Judit P
authors.initials: JP
authors.lastname: Szabó
authors.affiliation: Department of Medical Chemisty, University of Debrecen, Debrecen, Hungary;; MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Kovács
authors.affiliation: Department of Medical Chemisty, University of Debrecen, Debrecen, Hungary;; MTA-DE Lendület Laboratory of Cellular Metabolism, Debrecen, Hungary;; Research Center for Molecular Medicine, University of Debrecen, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Bai
authors.affiliation: Department of Medical Imaging, Nuclear Medicine, University of Debrecen, Debrecen, Hungary;; Scanomed LTD, Debrecen, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Trencsényi
keywords: 18FDG; 68Ga-NODAGA-PCA; B16-F10 tumor; Melanoma malignum; Positron Emission Tomography, Procainamide.