PET and planar imaging of tumor hypoxia with labeled metronidazole.
OBJECTIVE
This study was aimed to develop 99mTc- and 68Ga-labeled metronidazole (MN) using ethylenedicysteine (EC) as a chelator and evaluate their potential use to assess tumor hypoxia.


METHODS
EC-MN was labeled with 99mTc in the presence of tin (II) chloride. Labeling EC-MN with 68Ga was achieved by adding 68GaCl3 (2 mCi with 3.4 microg cold GaCl3). In vitro cellular uptakes of 99mTc- and 68Ga-EC-MN were obtained in various types of tumor cells at 0.5-4 hours. Tissue distribution and PET imaging of 99mTc and 68Ga-EC-MN were evaluated in breast tumor-bearing rats at 0.5-4 hours. Tumor oxygen tension was measured using an oxygen probe.


RESULTS
There were similar cellular uptakes (2-10%) between 99mTc- and 68Ga-EC-MN at 0.5-4 hours. In vivo biodistribution of 99mTc- and 68Ga-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Positron emission tomography images confirmed that the tumors could be visualized clearly with 68Ga-EC-MN. Oxygen tension in tumor tissue was determined to be 6-10 mm Hg compared with 40-50 mm Hg in normal muscle tissue.


CONCLUSIONS
The results indicated that it is feasible to use 99mTc- and 68Ga-EC-MN for assessment of tumor hypoxia. These agents may be useful in selecting and evaluating cancer therapy.
Ito
Megumi
M
Division of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Yang
David J
DJ
Mawlawi
Osama
O
Mendez
Richard
R
Oh
Chang-Sok
CS
Azhdarinia
Ali
A
Greenwell
Allison C
AC
Yu
Dong-Fang
DF
Kim
E Edmund
EE
D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D007553:Isotope Labeling / Q000379:methods; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D010100:Oxygen / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C514359:gallium-68-ethylenedicysteine-metronidazole; C514360:technetium 99m ethylenedicysteine-metronidazole; D008795:Metronidazole; D010100:Oxygen