title: Preclinical studies of [(99m)Tc]DTPA-mannosyl-dextran .
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.
authors.affiliation: Department of Radiology, University of California San Diego, La Jolla, CA 92093, USA. ckhoh@ucsd.edu
authors.forename: Carl K
authors.initials: CK
authors.lastname: Hoh
authors.forename: Anne M
authors.initials: AM
authors.lastname: Wallace
authors.forename: David R
authors.initials: DR
authors.lastname: Vera
mesh_terms: D000818:Animals; D001822:Body Burden; D002318:Cardiovascular Diseases / Q000209:etiology; D003911:Dextrans / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000633:toxicity; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000378:metabolism*; D018655:Lymphocyte Count; D008297:Male; D008351:Mannans / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000633:toxicity; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000633:toxicity; D004369:Pentetic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000633:toxicity; D011817:Rabbits; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000493:pharmacokinetics / Q000633:toxicity; D051381:Rats; D016019:Survival Analysis; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives; D014018:Tissue Distribution
chemical_list: D003911:Dextrans; D008351:Mannans; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C431884:technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate