UNLABELLED: 123I-Labeled iodoazomycin arabinoside (IAZA) is a marker of hypoxia in vivo. It has been used clinically to image hypoxic tissue in solid tumors, peripheral vascular disease of diabetic origin, blunt brain trauma, and rheumatoid joints and in an animal model of cerebrovascular disease. The radiation dose biodistribution for 123I-IAZA was studied to assess and characterize its suitability as a clinical radiopharmaceutical. METHODS: Six healthy volunteers each received a nominal 185-MBq (5 mCi) dose of 123I-IAZA administered as a slow (1-3 min) intravenous injection in the arm. Anterior and posterior whole-body planar images were acquired for each volunteer beginning immediately after injection and at 1-2, 3-4, 6-8, and 20-24 h after injection. Venous blood samples (0 h predose through 28 h after dosing) and 28-h cumulative urine samples were taken from each volunteer for pharmacokinetic analysis. Radiation dose estimates were performed for all volunteers, with "reference adult" (for men) and "adult female" (for women) phantoms, and both the International Commission on Radiological Protection 30 gastrointestinal tract model and the dynamic bladder model, using the MIRDOSE3 program. Two sets of estimates, 1 using a pharmacokinetic analysis of total serum radioactivity and 1 based on scintigraphic image data, were obtained for each volunteer after 123I-IAZA administration. RESULTS: Two compartments were discernible by pharmacokinetic analysis, and 4 compartments were discernible by image analysis. The urinary bladder wall received the greatest radiation dose (6.3E-02 +/- 8.7E-03 mGy/MBq), followed by the upper large intestinal wall (5.6E-02 +/- 1.2E-02 mGy/MBq), the lower large intestinal wall (5.0E-02 +/- 1.2E-02 mGy/MBq), and the thyroid (4.4E-02 +/- 1.4E-02 mGy/MBq). Approximately 90% of physiologically eliminated radioactivity was excreted through the kidneys. Radioactivity entering the intestinal tract from the gallbladder constituted <10% of biologically eliminated activity. CONCLUSION: The dosimetric analysis of 123I-IAZA in 6 healthy volunteers indicated that both disposition kinetics and radiation dosimetry support its clinical use for imaging tissue hypoxia.
UNLABELLED: 123I-Labeled iodoazomycin arabinoside (IAZA) is a marker of hypoxia in vivo. It has been used clinically to image hypoxic tissue in solid tumors, peripheral vascular disease of diabetic origin, blunt brain trauma, and rheumatoid joints and in an animal model of cerebrovascular disease. The radiation dose biodistribution for 123I-IAZA was studied to assess and characterize its suitability as a clinical radiopharmaceutical. METHODS: Six healthy volunteers each received a nominal 185-MBq (5 mCi) dose of 123I-IAZA administered as a slow (1-3 min) intravenous injection in the arm. Anterior and posterior whole-body planar images were acquired for each volunteer beginning immediately after injection and at 1-2, 3-4, 6-8, and 20-24 h after injection. Venous blood samples (0 h predose through 28 h after dosing) and 28-h cumulative urine samples were taken from each volunteer for pharmacokinetic analysis. Radiation dose estimates were performed for all volunteers, with "reference adult" (for men) and "adult female" (for women) phantoms, and both the International Commission on Radiological Protection 30 gastrointestinal tract model and the dynamic bladder model, using the MIRDOSE3 program. Two sets of estimates, 1 using a pharmacokinetic analysis of total serum radioactivity and 1 based on scintigraphic image data, were obtained for each volunteer after 123I-IAZA administration. RESULTS: Two compartments were discernible by pharmacokinetic analysis, and 4 compartments were discernible by image analysis. The urinary bladder wall received the greatest radiation dose (6.3E-02 +/- 8.7E-03 mGy/MBq), followed by the upper large intestinal wall (5.6E-02 +/- 1.2E-02 mGy/MBq), the lower large intestinal wall (5.0E-02 +/- 1.2E-02 mGy/MBq), and the thyroid (4.4E-02 +/- 1.4E-02 mGy/MBq). Approximately 90% of physiologically eliminated radioactivity was excreted through the kidneys. Radioactivity entering the intestinal tract from the gallbladder constituted <10% of biologically eliminated activity. CONCLUSION: The dosimetric analysis of 123I-IAZA in 6 healthy volunteers indicated that both disposition kinetics and radiation dosimetry support its clinical use for imaging tissue hypoxia.
Authors: Hans-S Jans; Daria Stypinski; Piyush Kumar; John R Mercer; Stephen A McQuarrie; Alexander J B McEwan; Leonard I Wiebe Journal: Pharmaceutics Date: 2022-08-09 Impact factor: 6.525