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

Abstract

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-F-fluoroethanol (2-F-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. Uptake of 2-F-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-F-FEtOH uptake was directly compared with the C-iodoantipyrine perfusion reporter, and the perfusion-modifying drugs nicotinamide, pentoxifylline, and hydralazine were used to manipulate tumor perfusion before 2-F-FEtOH quantification. Uptake of 2-F-FEtOH in 4T1 and 67NR tumors was consistent with known perfusion differences within and between these tumors. 2-F-FEtOH uptake corresponded well with C-iodoantipyrine and reflected the tumor perfusion-modifying effects of each drug. 2-F-FEtOH is a novel F-based radiotracer for investigating tumor perfusion with PET imaging. Quantification of 2-F-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.

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“…Furthermore, a higher number of CD31 positive endothelial cells in 67NR tumors that form vascular structures were visible, whereas these were fewer and more unorganized in 4T1 tumors. This observation has also been found in a study evaluating tumor perfusion with 2-18 F-Fluorethanol in these two tumor models, distinguishing areas of good and poor perfusion and correlating those with the CD31 expression (32). In both tumor models, the expression of CD31 decreased during progression, which has also been found in a study by Serganova et al (26).…”

“…more heterogenous phenotype of 4T1 tumors is reflected in K trans maps as well, with higher values in the periphery and lower values in the necrotic tumor center, in comparison to largely homogenous K trans maps of 67NR tumors (32). This was also found in a study evaluating 4T1 and 67NR tumors with second harmonic generation imaging and resonance Raman spectroscopy (34).…”

“…Thus, while inflow of the contrast agent was reduced in 4T1 tumors, extravasation was enhanced with albumin-binding gadofosveset, which extravasates through leaky vessel walls and is not transferred back into the intravascular space ( 33 ). The more heterogenous phenotype of 4T1 tumors is reflected in K trans maps as well, with higher values in the periphery and lower values in the necrotic tumor center, in comparison to largely homogenous K trans maps of 67NR tumors ( 32 ). This was also found in a study evaluating 4T1 and 67NR tumors with second harmonic generation imaging and resonance Raman spectroscopy ( 34 ).…”