Preclinical characterization of 18FD-FPHCys, a new amino acid-based PET tracer

The imaging potential of a new F-18-labelled methionine derivative, S-(3-[F-18]fluoropropyl)-d-homocysteine (F-18-D-FPHCys), and its selectivity for amino acid transporter subtypes were investigated in vitro and by imaging of human tumour xenografts. Expression of members of the system L (LAT isoforms 1-4 and 4F2hc) and ASCT (ASCT isoforms 1 and 2) amino acid transporter subclasses were assessed by quantitative real-time PCR in four human tumour models, including A431 squamous cell carcinoma, PC3 prostate cancer, and Colo 205 and HT-29 colorectal cancer lines. The first investigations for the characterization of F-18-D-FPHCys were in vitro uptake studies by comparing it with [1-C-14]-l-methionine (C-14-MET) and in vivo by PET imaging. In addition, the specific involvement of LAT1 transporters in F-18-D-FPHCys accumulation was tested by silencing LAT1 mRNA transcription with siRNAs. To determine the proliferative activity in tumour xenografts ex vivo, Ki-67 staining was used as a biomarker. A431 cells showed the highest F-18-D-FPHCys uptake in vitro and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention was observed with C-14-MET. F-18-D-FPHCys retention was strongly correlated with LAT1 expression both in vitro (R (2) = 0.85) and in vivo (R (2) = 0.99). Downregulation of LAT1 by siRNA inhibited F-18-D-FPHCys uptake, demonstrating a clear dependence on this transporter for tumour uptake. Furthermore, F-18-D-FPHCys accumulation mirrored cellular proliferation. The favourable properties of F-18-D-FPHCys make this tracer a promising imaging probe for detection of tumours as well as for the noninvasive evaluation and monitoring of tumour growth.© 2012, Springer.

Keywords

Tyrosine, Methionine, Tomography, In vitro, Neoplasms, Homocysteine

Citation

Denoyer, D., Kirby, L., Waldeck, K., Roselt, P., Neels, O.C., Bourdier, T., Shepherd, R., Katsifis, A., & Hicks, R.J. (2012). Preclinical characterization of f-18-d-fphcys, a new amino acid-based pet tracer. European Journal of Nuclear Medicine and Molecular Imaging, 39(4), 703-712. doi:10.1007/s00259-011-2017-4