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Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran .
- Source :
-
Nuclear medicine and biology [Nucl Med Biol] 2003 Jul; Vol. 30 (5), pp. 457-64. - Publication Year :
- 2003
-
Abstract
- We report the preclinical testing of a synthetic receptor-binding macromolecule, [(99m)Tc]DTPA-mannosyl-dextran (36 kDa, 8 DTPA and 55 mannosyl units per dextran, K(D) = 0.12 nM), for sentinel node detection. Nonclinical safety studies included cardiac pharmacology safety studies, acute toxicology and pathology studies at 50 and 500 times the scaled human dose in both rats and rabbits after foot pad administration, and perivascular irritation studies in rabbits following intra-muscular administration at 100 and 1000 times the scaled human dose. Biodistribution studies in rabbits at 15 m, 1 h, and 3 h indicated that [(99m)Tc]DTPA-mannosyl-dextran cleared the hind foot pad with a biological half-life of 2.21 +/- 0.27 h. Other than mild hepatocyte hypertrophy in rabbits, no abnormalities in toxicology or pathology were found. Intravenous administration had no effect on survival, any clinical observations, electrocardiograms, or blood pressures. Intramuscular injection had no effect on survival, clinical observations, injection site observations, or injection site histopathology. The estimated absorbed radiation dose to the affected breast was 0.15 mGy/MBq and the effective dose was 1.06 x 10(-2) mSv/MBq. This preclinical study demonstrates that [(99m)Tc]DTPA-mannosyl-dextran has no toxicities and has an acceptable biodistribution and radiation dose.
- Subjects :
- Animals
Body Burden
Cardiovascular Diseases etiology
Dextrans toxicity
Dogs
Drug Evaluation, Preclinical
Drug Stability
Female
Humans
Lymph Nodes diagnostic imaging
Lymphocyte Count
Male
Mannans toxicity
Models, Biological
Muscle, Skeletal drug effects
Muscle, Skeletal metabolism
Organ Specificity
Organotechnetium Compounds toxicity
Pentetic Acid toxicity
Rabbits
Radiation Dosage
Radionuclide Imaging
Radiopharmaceuticals adverse effects
Radiopharmaceuticals pharmacokinetics
Radiopharmaceuticals toxicity
Rats
Survival Analysis
Technetium Tc 99m Pentetate analogs & derivatives
Tissue Distribution
Dextrans adverse effects
Dextrans pharmacokinetics
Lymph Nodes metabolism
Mannans adverse effects
Mannans pharmacokinetics
Organotechnetium Compounds adverse effects
Organotechnetium Compounds pharmacokinetics
Pentetic Acid adverse effects
Pentetic Acid pharmacokinetics
Radiometry methods
Subjects
Details
- Language :
- English
- ISSN :
- 0969-8051
- Volume :
- 30
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nuclear medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 12831982
- Full Text :
- https://doi.org/10.1016/s0969-8051(03)00028-3