Amino acid metabolism is recognized as a target for medical imaging due to its increase in malignant cells. Several radiotracers with primary achievement and possible subsequent chances have been designed and tested to image
amino acid metabolism. Here, we report a new
amino acid conjugate, with the purpose of extending [99mTc][Tc-HYNIC/
EDDA]-Met(O) for single photon emission tomography (SPECT) imaging. The S-oxo-
l-methionine (Met(O))
amino acid hydrazinonicotinamide (HYNIC)
chelator conjugate (HYNIC-Met(O)) was prepared, using Fmoc solid-phase synthesis, and was radiolabeled with [99mTc]
technetium pertechnetate, using
tricine and
ethylenediamine-N,N-diacetic
acid (
EDDA) as co-
ligands. In vitro cellular uptake profile and saturation binding of radiotracer were determined on C6
glioma cells. Biodistribution and imaging studies were carried out on rat bearing C6
tumor tissue grafts. [99mTc][Tc-HYNIC/
EDDA]-Met(O) was prepared in high yield and radiochemical purity (>98 %). The partition coefficient result showed that radioconjugate was very hydrophilic. The radioconjugate indicated both high cell uptake and in vitro internalization. Low nanomolar dissociation constant (66.02 nM) in C6
glioma cells was obtained for it as well. [99mTc][Tc-HYNIC/
EDDA]-Met(O) revealed magnificent
tumor uptake at early time points, with 1.98 ± 0.33 % injected activity per gram
tumor (% IA/g) at 30 min post injection. The
tumor uptake continued for 1 and 2 h and was 0.45 ± 0.33 % IA/g at 4 h. The uptake in other organs decreased much more rapidly causing high
tumor to normal organ ratios so that the highest ratio of 13.25 of
tumor-to-muscle at 60 min after injection was obtained with high contrast in gamma imaging. These results point out a very favorable [99mTc]Tc-labeled
amino acid for targeting
amino acid metabolism through target system L
amino acid transporter (LAT1) in malignant cells especially C6
glioma cells. [99mTc][Tc-HYNIC/
EDDA]-Met(O) manifests extremely good distribution, excretion and imaging attributes. So it seems to be an appropriate nominate for clinical imaging.