NDLI: Noninvasive Assessment of Tumor Hypoxia with 99mTc Labeled Metronidazole

Content Provider	Springer Nature Link
Author	Yang, David J. Ilgan, Seyfettin Higuchi, Tetsuya Zareneyrizi, Fereshteh Oh, Chang Sok Liu, Chun Wei Kim, E. Edmund Podoloff, Donald A.
Copyright Year	1999
Abstract	Purpose. The assessment of tumor hypoxia by imaging modality prior to radiation therapy would provide a rational means of selecting patients for treatment with radiosensitizers or bioreductive drugs. This study aimed to develop a $^{99m}$Tc-labeled metronidazole (MN) using ethylene-dicysteine (EC) as a chelator and evaluate its potential use to image tumor hypoxia. Methods. EC was conjugated to amino analogue of MN using Sulfo-N-hydroxysuccinimide and l-ethyl-3-(3-dimethylaminopropyl) carbodiimide-HCl as coupling agents, the yield was 55%. Tissue distribution of $^{99m}$Tc-EC-MN was determined in breast tumor-bearing rats at 0.5, 2, and 4 hrs. Planar imaging and whole-body autoradiograms were performed. The data was compared to that using $^{99m}$Tc-EC (control), [$^{l8}$F]fluoromisonidazole (FMISO) and [$^{131}$I] iodomisonidazole (IMISO). Results. In vivo biodistribution of $^{99m}$Tc-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle ratios as a function of time. Conversely, tumor-to-blood values showed time-dependent decrease with $^{99m}$Tc-EC in the same time period. Planar images and autoradiograms confirmed that the tumors could be visualized clearly with $^{99m}$Tc-EC-MN from 0.5 to 4 hrs. There was no significant difference of tumor-to-blood count ratios between $^{99m}$Tc-EC-MN and [$^{131}$I]IMISO at 2 and 4 hrs postinjection. From 0.5 to 4 hrs, both $^{99m}$Tc-EC-MN and [$^{131}$I]IMISO have higher tumor-to-muscle ratios compared to [$^{18}$]FMISO. Conclusions. It is feasible to use $^{99m}$Tc-EC-MN to image tumor hypoxia.
Starting Page	743
Ending Page	750
Page Count	8
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	16
Issue Number	5
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1999-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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