Radiosynthesis of [¹⁸F]-fluorobenzoate-doxorubicin using acylation approach

Background: Previously, we have labeled doxorubicin with [^99mTc] and evaluated its potential as a SPECT agent to detect cancer in tumor bearing mice. In this study, we sought to radiolabel doxorubicin with [¹⁸F] using acylation method. Methods: A quaternary salt of the precursor pentamethylbenzyl-4-(trimethylammonium trifluoromethanesulfonate) benzoate was synthesized and characterized by 1H-NMR. As a first step, 4-[¹⁸F]- fluorobenzoic acid (FBA) was synthesized from precursor. In second step, [¹⁸F]-FBA was further converted to its corresponding acyl form to radiolabel doxorubicin via acylation reaction. Results: The total reaction time for the synthesis of [¹⁸F]-fluorobenzoate-doxorubicin was about 60 minutes. The radiolabeling efficiency of the final product was estimated to be about 59.0% The radiochemical yield for the synthesis of [¹⁸F]-FBA and [¹⁸F]-fluorobenzoate-doxorubicin were 19.0-29.0% and 12.0-14.0% respectively. Conclusion: Radio synthesis of [¹⁸F]-fluorobenzoate-doxorubicin by acylation is a convenient method. However, further improvement in the labeling strategy is required to increase the radiolabeling efficiency and radio synthesis yield. Also, the radiolabeled product needs a detailed pre-clinical evaluation.