D- and L- enantiomers of 2- and 6-FDOPA for melanoma imaging

Objectives Investigate the feasibility of D- and L-enantiomers of [¹⁸F]-labelled 2- and 6-FDOPA for melanoma imaging.

Methods D- and L-enantiomers of [¹⁸F]2- and 6-FDOPA were prepared by the direct fluorination of DOPA. 20 mBq of each tracer (0.2 mL) was injected into the tail veins of mice bearing B16-F10 mealnoma tumor after they were anesthetized with isoflurane. Animals were imaged using a Philips Mosaic small animal PET scanner followed by the CT component of a SPECT/CT scanner for co-registration. B16-F10 melanoma cells, grown in complete MEM/F11 medium, were incubated with 55 mBq of [¹⁸F]2- and 6-FDOPA (D- and L-) for 120 min at 37 ^oC. Following centrifugation, cells were separated from the culture medium and thoroughly washed with HBSS buffer until less than 10% of the total ¹⁸F remained in the supernatant. Percent uptake of FDOPA isomers in tumor cells was calculated based on the ¹⁸F activity measured in each component.

Results Fluorine-18 uptake in the tumor cells for 2-F-L-DOPA (20.5%) was considerably higher compared to 2-F-D-DOPA (7.9%). Itwas comparable between 6-F-D-DOPA (17%) and 6-F-L-DOPA (19%). PET images of B16-F10 melanoma bearing mice showed clear delineation of the tumor 120 min after injection with [¹⁸F] labelled 6-F-D-DOPA and 2-F-L-DOPA.

Conclusions Both [¹⁸F] labelled 6-D-DOPA and 2-F-L-DOPA appeared to be promising tracers for the delineation of melanoma. [¹⁸F]6-F-D-DOPA may not be metabolised in vivo causing a higher signal to noise ratio in tumor images. Relaitively higher upatke of [¹⁸F]2-F-L-DOPA may be due its incorporation into melanin by the Raper-Mason Scheme for melanogenesis.

Research Support Authors acknowledge Dr. Karen Gulenchyn and Ms. Carol Dunne of HHS for their support.