Development and Evaluation of [ 68 Ga]Ga-Labeled Riboflavin Derivative for RFVT3-Targeted PET Imaging of Melanoma in Mice.

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  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Chemical Society, c2004-
    • Subject Terms:
      Gallium Radioisotopes* ; Positron-Emission Tomography*/methods ; Riboflavin*/chemistry ; Melanoma, Experimental*/diagnostic imaging ; Melanoma, Experimental*/metabolism; Animals ; Mice ; Cell Line, Tumor ; Tissue Distribution ; Mice, Inbred C57BL ; Radiopharmaceuticals/chemistry ; Radiopharmaceuticals/pharmacokinetics ; Melanoma/diagnostic imaging ; Melanoma/metabolism ; Melanoma/pathology ; Melanoma/drug therapy
    • Abstract:
      The limited progress in treatment options and the alarming survival rates in advanced melanoma emphasize the significant research importance of early melanoma diagnosis. RFVT3, a crucial protein at the core of energy metabolism reprogramming in melanoma, might play a pivotal role in early detection. In this study, [ 68 Ga]Ga-NOTA-RF, based on riboflavin (RF), was rationally developed and validated, serving as an innovative tool for positron emission tomography (PET) imaging of RFVT3 expression in melanoma. The in vitro assays of RFVT3 specificity of [ 68 Ga]Ga-NOTA-RF were performed on B16F10 melanoma cells. Then, PET imaging of melanoma was investigated in B16F10 allograft mouse models with varying volumes. Biodistribution studies are used to clarify the behavior of [ 68 Ga]Ga-NOTA-RF in vivo . [ 68 Ga]Ga-NOTA-RF was obtained with high radiochemical purity (>95%). A significant uptake (37.79 ± 6.86%, n = 4) of [ 68 Ga]Ga-NOTA-RF was observed over time in B16F10 melanoma cells, which was significantly inhibited by RFVT3 inhibitors RF or methylene blue (MB), demonstrating the specific binding of [ 68 Ga]Ga-NOTA-RF. At 60 min postinjection, the tumor-to-muscle (T/M) ratio of [ 68 Ga]Ga-NOTA-RF was 4.03 ± 0.34, higher than that of the RF-blocked group (2.63 ± 0.19) and MB-blocked group (2.14 ± 0.20). The T/M ratios for three distinct tumor volumes-small (5 mm), medium (10 mm), and large (15 mm) were observed to be 5.25 ± 0.28, 4.03 ± 0.34, and 3.19 ± 0.55, respectively. The expression of RFVT3 was validated by immunohistochemical staining in various tumor models, with small B16F10 tumors exhibiting the highest expression. [ 68 Ga]Ga-NOTA-RF demonstrates promising properties for the early diagnosis of melanoma and the examination of minute metastatic lesions, indicating its potential to assist in guiding clinical treatment decisions.
    • Contributed Indexing:
      Keywords: PET imaging; RFVT3; melanoma; riboflavin
    • Accession Number:
      0 (Gallium Radioisotopes)
      TLM2976OFR (Riboflavin)
      0 (Radiopharmaceuticals)
    • Publication Date:
      Date Created: 20240916 Date Completed: 20241007 Latest Revision: 20241008
    • Publication Date:
      20241009
    • Accession Number:
      10.1021/acs.molpharmaceut.4c00209
    • Accession Number:
      39279392