⁵²Mn-labelled Beta-cyclodextrin for Melanoma Imaging: A Proof-of-concept Preclinical Study

Background/Aim: As prostaglandin E2 (PGE2) and its receptors (EP2) are over-expressed on tumor cells and microenvironment, radiolabeled cyclodextrins targeting such biomolecules are valuable vector candidates in molecular cancer diagnostics. Using experimental melanoma models, we evaluated the in vivo imaging behavior of novel Manganese-52-labeled (⁵²Mn) randomly methylated beta-cyclodextrin ([⁵²Mn]Mn-DOTAGA-RAMEB) and compared it with the following well-established tumor-specific probes: melanocortin-1 receptor (MC1-R)-affine [⁶⁸Ga]Ga-DOTA-NAPamide and PGE2 selective [⁶⁸Ga]Ga-DOTAGA-RAMEB cyclodextrin. Materials and Methods: Post-injection of [⁶⁸Ga]Ga-DOTA-NAPamide, [⁶⁸Ga]Ga-DOTAGA-RAMEB, and [⁵²Mn]Mn-DOTAGA-RAMEB into MC1-R positive B16F10 melanoma-bearing mice, tumor radio-pharmaceutical uptake was quantified in vivo and ex vivo using preclinical positron emission tomography (PET) and high-performance gamma counter. Results: Although all tracers performed well in tumor identification, the highest standardized uptake values were detected in the [⁶⁸Ga]Ga-DOTA-NAPamide scans. Corresponding to the ex vivo data, meaningful [⁵²Mn]Mn-DOTAGA-RAMEB accumulation 1 h post-injection confirmed the tumor-targeting potential of the tracer. Temporal changes in PGE2/EP2 expression of the neoplasms may explain the significant differences observed between the tumor uptake of the two cyclodextrin probes and that of the ⁵²Mn-labelled compound measured 1 h, 4 h, and 3 days post-injection (p≤0.01, p≤0.05). Conclusion: Although further pharmacokinetical optimization may be required, ⁵²Mn-labelled cyclodextrin holds potential in melanoma diagnostics and the PET-based longitudinal assessment of tumor-associated PGE2/EP2 expression.