Preliminary studies of 99mTc-BnAO and its analogues: synthesis, radiolabeling and in vitro cell uptake.
BACKGROUND
(99m)Tc-BnAO is one of the nonnitroimidazole hypoxia markers with the highest citation and could be potentially useful in both oncology and other clinical applications. However, it appears inferior in vitro due to lower absolute accumulation and smaller anoxic/normoxic uptake ratio. It is possible that the analogues of (99m)Tc-BnAO have higher hypoxia selectivity after the ligand of (99m)Tc-BnAO is modified.


METHODS
2,2'-(1,4-Diaminobutane)bis(2-methyl-3-butanone) dioxime (BnAO or HL91) and three novel analogues were synthesized and radiolabeled with technetium-99m. The cellular uptake of the radiolabeled complexes was determined in murine sarcoma S180 cell lines under anoxic and normoxic conditions.


RESULTS
(99m)Tc-BnAO and its three novel analogues continuously accumulated in anoxic cells but not in normoxic ones, while the analogues showed earlier hypoxia selectivity and greater anoxic/normoxic differential.


CONCLUSIONS
The analogues are superior to (99m)Tc-BnAO in terms of in vitro hypoxia selectivity and are viable candidates for further development as new nonnitroimidazole hypoxia markers in the future.
Sun
Xin
X
Beijing National Laboratory for Molecular Sciences (BNLMS), Department of Applied Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Chu
Taiwei
T
Wang
Xiangyun
X
D000818:Animals; D001692:Biological Transport; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002477:Cells / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D021241:Spectrometry, Mass, Electrospray Ionization; D013667:Technetium / Q000737:chemistry*; D044366:Transition Temperature
D015609:Organotechnetium Compounds; D010091:Oximes; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime; D013667:Technetium