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Eur J Nucl Med Mol Imaging. 2012 Apr;39(4):703-12. doi: 10.1007/s00259-011-2017-4. Epub 2011 Dec 13.

Preclinical characterization of 18F-D-FPHCys, a new amino acid-based PET tracer.

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  • 1Molecular Imaging and Targeted Therapeutics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Delphine.Denoyer@petermac.org

Abstract

PURPOSE:

The imaging potential of a new (18)F-labelled methionine derivative, S-(3-[(18)F]fluoropropyl)-D-homocysteine ((18)F-D-FPHCys), and its selectivity for amino acid transporter subtypes were investigated in vitro and by imaging of human tumour xenografts.

METHODS:

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 (18)F-D-FPHCys were in vitro uptake studies by comparing it with [1-(14)C]-L-methionine ((14)C-MET) and in vivo by PET imaging. In addition, the specific involvement of LAT1 transporters in (18)F-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.

RESULTS:

A431 cells showed the highest (18)F-D-FPHCys uptake in vitro and in vivo followed by Colo 205, PC3 and HT-29. A similar pattern of retention was observed with (14)C-MET. (18)F-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 (18)F-D-FPHCys uptake, demonstrating a clear dependence on this transporter for tumour uptake. Furthermore, (18)F-D-FPHCys accumulation mirrored cellular proliferation.

CONCLUSION:

The favourable properties of (18)F-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.

PMID:
22160176
[PubMed - indexed for MEDLINE]
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