Searching for diagnostic properties of novel fluorine-18-labeled D-allose

Two fluorine-18-labeled analogues, 3-deoxy-3-[¹⁸F]fluoro-D-allose (3-[¹⁸F]FDA) and 6-deoxy-6-[¹⁸F]fluoro-D-allose (6-[¹⁸F]FDA), were synthesized and their potentials of diagnostic property were characterized.

In vitro rat red blood cell (RBC) transport and phosphorylation by yeast hexokinase were evaluated in comparison with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG). The rate of protein binding in pooled human serum was measured by an ultrafiltration method. In vivo metabolite analysis in mice was also performed. Biodistribution, urine excretion, and in vivo renal kinetics in mice were compared with 2-deoxy-2-[¹⁸F]fluorosorbitol ([¹⁸F]FDS).

Rat RBC uptake of 3- and 6-[¹⁸F]FDA (7.8 ± 2.5%ID and 10.2 ± 4.8%ID, respectively) was significantly lower than that of [¹⁸F]FDG (44.7 ± 8.7%ID). RBC uptake of 3-[¹⁸F]FDA was inhibited by D-glucose (30%) and cytochalasin B (40%), indicating the involvement of GLUT1-dependent transport. In contrast, 6-[¹⁸F]FDA transport was not inhibited by D-glucose and cytochalasin B. 3- and 6-[¹⁸F]FDA were not phosphorylated by yeast hexokinase under the conditions that result in 60% conversion of [¹⁸F]FDG into [¹⁸F]FDG-6-phosphate within 30 min. Serum protein binding of 3- and 6-[¹⁸F]FDA was negligible. Metabolic transformation of both tracers was not detected in plasma and urine at 30 min after injection. The highest tissue uptake of both tracers was observed in kidneys. Heart and brain uptake of both tracers was below blood levels throughout the biodistribution studies (until 120 min after injection). No significant uptake in the bone was observed, indicating the absence of de-fluorination in mice. In vivo PET imaging visualized rapid excretion of the administered 3- and 6-[¹⁸F]FDA from the kidneys, with minimal tracer accumulation in other organs. The urine excretion rate of 3-[¹⁸F]FDA was much lower than that of 6-[¹⁸F]FDA and [¹⁸F]FDS.

3- and 6-[¹⁸F]FDA might be unsatisfactory for tumor imaging. In contrast, these tracers demonstrated high levels of kidney uptake and excretion, low serum protein binding, and high metabolic stability as preferable properties for renal imaging. Notably, the urine excretion rate and kidney uptake kinetics of 6-[¹⁸F]FDA were comparable with those of the potential renal imaging agent [¹⁸F]FDS. Further validation studies in animal models are required to confirm the feasibility of 6-[¹⁸F]FDA as a functional renal imaging agent.