Abstract | BACKGROUND: METHODS: High-specific-activity [(131)I] IAZA was prepared in therapeutic doses (up to 3 GBq per batch) by isotope exchange in pivalic acid melt and was purified on Sep-Pak cartridges. Stability in 15% ethanol in saline at 4 degrees C was determined by high-performance liquid chromatography. IAZA cytotoxicity (IC(50), approximately 0.1 mM) against both murine (EMT-6) and human (143B, 143B-LTK) tumor cells determined by MTT test was in the range previously reported for EMT-6 cells using a clonogenic assay. Tissue radioactivity levels were measured in a murine tumor model for the 24- to 168-h postinjection period. Radiation dose estimates obtained from the tissue activity levels for this period were calculated from pharmacokinetic (WinNonlin) and dosimetry (MIRD and RAdiation Dose Assessment Resource) parameters. RESULTS: The radioiodination efficiency was >90%, but with systematic losses during Sep-Pak purification, the recovered yields of [(131)I] IAZA were approximately 75%. The product (specific activity, 4.6-6.4 GBq/micromol) was stable for at least 2 weeks, with only approximately 6% degradation over this storage period. Extended biodistribution studies in Balb/c mice bearing implanted EMT-6 tumors showed that the highest tumor/blood radioactivity ratio (T/B; 4.8) occurred 24 h after dosing; the T/B ratio was approximately 1.5 at the end of the 7-day study. The 24- to 168-h tissue radioactivity data fit a one-compartment model except for liver data, which best fit a two-compartment model. Dosimetry estimates showed a tumor self-dose of 7.4 mGy/MBq, which is several-fold higher than for the liver or the kidney. CONCLUSIONS: [(131)I] IAZA can be efficiently radiolabeled at high specific activity, purified by a simple Sep-Pak technique and stored with little radiolysis or chemical decomposition at these specific activities. Based on measured radioactivity burdens during the week following injection and on published animal ([(125)I] IAZA) and clinical ([(123)I] IAZA) dosimetry data, the current dose estimates point to selective tumor irradiation at low dose rates.
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Authors | Piyush Kumar, Steven A McQuarrie, Aihya Zhou, Alexander J B McEwan, Leonard I Wiebe |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 32
Issue 6
Pg. 647-53
(Aug 2005)
ISSN: 0969-8051 [Print] United States |
PMID | 16026712
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Iodine Radioisotopes
- Nitroimidazoles
- Radiopharmaceuticals
- Tetrazolium Salts
- Thiazoles
- iodoazomycin arabinoside
- thiazolyl blue
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Topics |
- Animals
- Cell Hypoxia
- Cell Proliferation
- Female
- Humans
- Iodine Radioisotopes
(pharmacokinetics, therapeutic use)
- Mammary Neoplasms, Experimental
(metabolism, radiotherapy)
- Metabolic Clearance Rate
- Mice
- Mice, Inbred BALB C
- Nitroimidazoles
(pharmacokinetics, therapeutic use)
- Radioimmunotherapy
- Radiometry
- Radiopharmaceuticals
(pharmacokinetics, therapeutic use)
- Radiotherapy Dosage
- Tetrazolium Salts
- Thiazoles
- Tissue Distribution
- Tumor Cells, Cultured
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