2-¹⁸F-Fluoroethanol Is a PET Reporter of Solid Tumor Perfusion

Solid tumor perfusion is a proven variable of interest for predicting cancer aggression and response to therapy. Current methods for noninvasively imaging tumor perfusion with PET are limited by restricted accessibility and short half-lives of perfusion radiotracers. This study presents 2-¹⁸F-fluoroethanol (2-¹⁸F-FEtOH) as a perfusion reporter that can distinguish between tumors of varying perfusion levels and can be applied to screening drugs that modify tumor perfusion. Methods: Uptake of 2-¹⁸F-FEtOH in 4T1 and 67NR murine mammary carcinoma tumors grown in mice was measured using ex vivo radiography as well as static and dynamic PET imaging. 2-¹⁸F-FEtOH uptake was directly compared with the ¹⁴C-iodoantipyrine perfusion reporter, and the perfusion-modifying drugs nicotinamide, pentoxifylline, and hydralazine were used to manipulate tumor perfusion before 2-¹⁸F-FEtOH quantification. Results: Uptake of 2-¹⁸F-FEtOH in 4T1 and 67NR tumors was consistent with known perfusion differences within and between these tumors. 2-¹⁸F-FEtOH uptake corresponded well with ¹⁴C-iodoantipyrine and reflected the tumor perfusion-modifying effects of each drug. Conclusion: 2-¹⁸F-FEtOH is a novel ¹⁸F-based radiotracer for investigating tumor perfusion with PET imaging. Quantification of 2-¹⁸F-FEtOH uptake can be used to distinguish between tumors of varying perfusion and to screen the efficacy of blood flow-modifying drugs for use as adjuvants to existing cancer therapies.