3-O-Methyl-6-[¹⁸F]fluoro-L.DOPA ([¹⁸F]OMFD): Development and first application of a new tracer for tumor detection with PET.

OBJECTIVES: Development (synthesis, biologic evaluation and first results in humans) of a [¹⁸F]-labeled synthetic amino acid for tumor detection with PET.

METHODS: Synthesis of [¹⁸F]OMFD based on a new precursor (N-formyl-3-O-methyl-4-O-Boc-6-trimethylstannyl-L-DOPA-ethyl-ester). The biologic evaluation was performed in cell culture (HT-29;RBE-4) and tumor bearing nude mice (SC-Ca). First application in humans were obtained in 4 patients with recurrent glioblastoma multiforme with inconclusive CT and MRI. [¹⁸F]OMFD was used to identify localization and extent of recurrent tumor for treatment planning with stereotactic radiotherapy, which was the last treatment option for the individual patient.

RESULTS: The radiochemical yield of [¹⁸F]OMFD was 20-25% (decay corrected, related to [¹⁸F]F₂) in 50 min synthesis time. Cell culture experiments showed a high tracer uptake in tumor cells via the L-amino acid transporter without evidence for any metabolism or protein incorporation. Biodistribution in mice 60 min p.i. showed a high tumor uptake (12.4 ± 1.8%ID/g) with a high tumor/blood ratio (9.2 ± 0.845 min p.i.). In all patients an increased tracer uptake in the area of the suspected recurrence (lesion to non-lesion 2.2 ± 0.5) was found. In the whole body scan only little tracer uptake was observed in the muscles, thorax and abdomen.

CONCLUSION: In vitro and in vivo experiments showed increased [¹⁸F]OMFD uptake in tumor tissue. The results of preliminary diagnostic studies with [¹⁸F]OMFD in patients with glioblastoma multiforme indicate its potential for tumor imaging.