A micro-PET/CT approach using O-(2-[18F]fluoroethyl)-l-tyrosine in an experimental animal model of F98 glioma for BNCT

A number of recent applications demonstrated the potentiality of radiolabeled aromatic amino acids for brain tumor imaging with positron emission tomography (PET). The uptake mechanism of these molecules is similar to other metabolic substrate and it is based on their preferential accumulation in neoplastic cells, presumably linked to an increased expression of amino acid transporters but not their incorporation in proteins (Jacobs et al., 2005; McConathy et al. 2008; Menichetti et al., 2009). In Boron Neutron Capture Therapy (BNCT) the assessment of the actual boron distribution is performed by PET using the tracer 4-dihydroxyboryl-2-[18F]fluoro-d,l-phenylalanine (18F-BPA) ( [Aihara et al., 2006], [Ariyoshi et al., 2007], [Kankaanranta et al., 2007], [Kabalka et al., 2003] and [Daquino et al., 2004]). Its pharmacokinetics is assumed to be very close to that of BPA, because of its structural similarity. In this work, an alternative to 18F-BPA/PET has been investigated: O-(2-18F-fluoroethyl)-d,l-tyrosine (18F-FET, more commonly FET). FET is a 18F-labeled amino acid (Hamacher and Coenen, 2002) applied in neurooncology; this tracer demonstrated high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging ( [Ishiwata et al., 2004], [Mehrkens et al., 2008], [Langen et al., 2006] and [Pauleit et al., 2009]). FET labeling is performed using 18F-fluoride (109.7 min half-life), the most convenient form of fluorine-18 currently used for the preparation of PET radiopharmaceuticals. The use of fluoride ion offers an improvement over the use of molecular 18F-F2, which is used for labeling BPA. Molecular fluorine is highly reactive and difficult to work with and is available in only a few PET centers, outfitted with the special equipment and cyclotron targets. This study focused on the use of FET to screen tumor lesions in experimental model using a small field of view PET. Our micro-PET–FET approach could lead to the assessment of the transport and the net influx and accumulation of FET, considered BPA analog. Since micro-PET and micro-CT are able to integrate in the same framework anatomical and functional imaging, it is possible to study the distribution of FET as mimic of BPA in tumor and healthy tissue. A correlation between BPA and FET pharmacokinetic, mainly linked to different affinities of transporters, could give numeric parameters useful for the prediction of boron loading in tumor and healthy tissues. The present study was performed on F98 tumor bearing rats at the 3rd week after the implantation.