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Development of (99m)Tc-N4-NIM for molecular imaging of tumor hypoxia.

Ali MS, Kong FL, Rollo A, Mendez R, Kohanim S, Smith DL, Yang DJ - J. Biomed. Biotechnol. (2012)

Bottom Line: Cell uptake of (99m)Tc-N4-NIM was higher than (99m)Tc-N4 in both cell lines.Biodistribution of (99m)Tc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time.Efficient synthesis of N4-NIM was achieved. (99m)Tc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. mohammad.ali@mdanderson.org

ABSTRACT
The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4,8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for (99m)Tc. The present study was aimed to develop (99m)Tc-cyclam-2-nitroimidazole ((99m)Tc-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of (99m)Tc-N4-NIM and (99m)Tc-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of (99m)Tc-N4-NIM was evaluated in breast-tumor-bearing rats at 0.5-4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of (99m)Tc-N4-NIM was >96% by HPLC. Cell uptake of (99m)Tc-N4-NIM was higher than (99m)Tc-N4 in both cell lines. Biodistribution of (99m)Tc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6-10 mmHg compared to 40-50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with (99m)Tc-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. (99m)Tc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.

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Planar scintigraphy of  99mTc-N4-NIM (15 mCi/rabbit, iv, acquired 500,000 count) showed higher tumor-to-muscle count density ratio (counts/pixel) at 60 and 120 min.
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fig5: Planar scintigraphy of  99mTc-N4-NIM (15 mCi/rabbit, iv, acquired 500,000 count) showed higher tumor-to-muscle count density ratio (counts/pixel) at 60 and 120 min.

Mentions: The selected planar scintigraphic images of tumor-bearing rats and rabbits after  99mTc-N4-NIM injection are shown in Figures 4 and 5. Tumors could be clearly detected by 99mTc-N4-NIM. The T/M ratios at 60–120 minutes were 4.1–4.2 in tumor-bearing rats and 2.52–2.98 in tumor-bearing rabbits, respectively.


Development of (99m)Tc-N4-NIM for molecular imaging of tumor hypoxia.

Ali MS, Kong FL, Rollo A, Mendez R, Kohanim S, Smith DL, Yang DJ - J. Biomed. Biotechnol. (2012)

Planar scintigraphy of  99mTc-N4-NIM (15 mCi/rabbit, iv, acquired 500,000 count) showed higher tumor-to-muscle count density ratio (counts/pixel) at 60 and 120 min.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376529&req=5

fig5: Planar scintigraphy of  99mTc-N4-NIM (15 mCi/rabbit, iv, acquired 500,000 count) showed higher tumor-to-muscle count density ratio (counts/pixel) at 60 and 120 min.
Mentions: The selected planar scintigraphic images of tumor-bearing rats and rabbits after  99mTc-N4-NIM injection are shown in Figures 4 and 5. Tumors could be clearly detected by 99mTc-N4-NIM. The T/M ratios at 60–120 minutes were 4.1–4.2 in tumor-bearing rats and 2.52–2.98 in tumor-bearing rabbits, respectively.

Bottom Line: Cell uptake of (99m)Tc-N4-NIM was higher than (99m)Tc-N4 in both cell lines.Biodistribution of (99m)Tc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time.Efficient synthesis of N4-NIM was achieved. (99m)Tc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. mohammad.ali@mdanderson.org

ABSTRACT
The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4,8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for (99m)Tc. The present study was aimed to develop (99m)Tc-cyclam-2-nitroimidazole ((99m)Tc-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of (99m)Tc-N4-NIM and (99m)Tc-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of (99m)Tc-N4-NIM was evaluated in breast-tumor-bearing rats at 0.5-4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of (99m)Tc-N4-NIM was >96% by HPLC. Cell uptake of (99m)Tc-N4-NIM was higher than (99m)Tc-N4 in both cell lines. Biodistribution of (99m)Tc-N4-NIM showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6-10 mmHg compared to 40-50 mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with (99m)Tc-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. (99m)Tc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy.

Show MeSH
Related in: MedlinePlus