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.
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 humantumour 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 humantumour 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.
Authors: Jung Hoon Yoon; In Jin Kim; Hyun Kim; Heung-Joong Kim; Moon Jin Jeong; Sang Gun Ahn; Soo A Kim; Chong Heon Lee; Bong Kyu Choi; Jong-Keun Kim; Kyu Yong Jung; Seoul Lee; Yoshikatsu Kanai; Hitoshi Endou; Do Kyung Kim Journal: Cancer Lett Date: 2004-11-05 Impact factor: 8.679
Authors: Thomas Bourdier; Rachael Shepherd; Paula Berghofer; Timothy Jackson; Christopher J R Fookes; Delphine Denoyer; Donna S Dorow; Ivan Greguric; Marie-Claude Gregoire; Rodney J Hicks; Andrew Katsifis Journal: J Med Chem Date: 2011-02-25 Impact factor: 7.446