Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET molecular imaging probe.
OBJECTIVE
The new tumor probe 5-([C]-methyloxy)-L-tryptophan ([C]-L-CMTP) had been found to show high uptake in tumor tissue in our previous report; however, the pharmacokinetic properties of [C]-L-CMTP have not been characterized. In this present study, we evaluated the potential of [C]-L-CMTP as a PET probe for tumor imaging.


METHODS
The biodistribution of [C]-L-CMTP was determined in healthy mice and the incorporation of [C]-L-CMTP into proteins was investigated. In-vitro competitive inhibition experiments were conducted with Hepa1-6 hepatoma cell lines. [C]-L-CMTP PET imaging was performed on S180 tumor-bearing mice and lung tumor-bearing mice.


RESULTS
Biodistribution studies showed high uptake of [C]-L-CMTP in the liver, kidney, and pancreas, but low uptake in brain. The transport assay studies in Hepa1-6 cells suggested that [C]-L-CMTP was mainly transported by the amino acid transport system B and LAT1. [C]-L-CMTP was not incorporated into proteins in vitro. PET imaging showed that [C]-L-CMTP had high uptake in S180 fibrosarcoma tumor and lung tumor.


CONCLUSIONS
[C]-L-CMTP was not incorporated into proteins and was mainly transported by the amino acid transport system B and LAT1, PET imaging showed that [C]-L-CMTP had high uptake in tumor models; it seemed to be a promising PET probe for tumor by LAT1 transport. Video abstract: http://links.lww.com/NMC/A70.
aPET Center, Guangdong General Hospital (Guangdong Academy of Medical Sciences) bDepartment of Nuclear Medicine, PET-CT Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Shanzhen
S
He
Ganghua
G
Tang
Kongzhen
K
Hu
Shuxia
S
Wang
Tingting
T
Huang
Xiang
X
Liang
D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods; D015335:Molecular Probes / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D015335:Molecular Probes; D019275:Radiopharmaceuticals; D014364:Tryptophan