Synthesis, radiolabeling and biological evaluation of propylene amine oxime complexes containing nitrotriazoles as hypoxia markers.
Two propylene amine oxime (PnAO) complexes, 1, containing a 3-nitro-1,2,4-triazole and 2, containing two 3-nitro-1,2,4-triazoles, were synthesized and radiolabeled with (99m)Tc in high labeling yields. Cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were tested using a S180 cells line. Under anoxic conditions, the cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were 33.7 ± 0.2% and 35.0 ± 0.7% at 4 h, whereas the normoxic uptakes of the two complexes were 6.0 ± 1.6% and 4.6 ± 0.9%, respectively. Both (99m)Tc-1 and (99m)Tc-2 displayed significant anoxic/normoxic differentials. The cellular uptakes were highly dependent on oxygen and temperature. Biodistribution studies revealed that both (99m)Tc-1 and (99m)Tc-2 showed a selective localization in tumor and slow clearance from it. At 4 h, the tumor-to-muscle ratios (T/M) were 3.79 for (99m)Tc-1 and 4.58 for (99m)Tc-2. These results suggested that (99m)Tc-labeled PnAO complexes (99m)Tc-1 and (99m)Tc-2 might serve as novel hypoxia markers. By introducing a second nitrotriazole redox center, the hypoxic accumulation of the marker was slightly enhanced.
Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Huafan
H
Huang
Lei
L
Mei
Taiwei
T
Chu
D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D011786:Quality Control; D019690:Technetium Tc 99m Exametazime / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D014018:Tissue Distribution; D014230:Triazoles / Q000737:chemistry
D015415:Biomarkers; D015609:Organotechnetium Compounds; D014230:Triazoles; D019690:Technetium Tc 99m Exametazime