Biological comparison of 149Pm-, 166Ho-, and 177Lu-DOTA-biotin pretargeted by CC49 scFv-streptavidin fusion protein in xenograft-bearing nude mice.
The radiolanthanides (149)Pm, (166)Ho, and (177)Lu possess a range of half-lives and alpha(-) beta(-) energies for targeted radiotherapy of cancer. (149)Pm-, (166)Ho-, and (177)Lu-DOTA-biotin were pretargeted to LS174T colorectal tumors in nude mice with CC49 scFvSA antibody-streptavidin fusion protein. Tumor uptakes of (149)Pm (22.9% ID/g), (166)Ho (30.2% ID/g), and (177)Lu (35.4% ID/g) peaked at 1-4 h. Rapid blood disappearance was accompanied by urinary excretion of 59-66% ID within 1 h. Biodistributions of these agents show promise for pretargeted radioimmunotherapy of cancer.
Lewis
Michael R
MR
Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, MO 65211, USA. LewisMic@missouri.edu
Zhang
Jiuli
J
Jia
Fang
F
Owen
Nellie K
NK
Cutler
Cathy S
CS
Embree
Mary F
MF
Schultz
Jody
J
Theodore
Louis J
LJ
Ketring
Alan R
AR
Jurisson
Silvia S
SS
Axworthy
Donald B
DB
D000818:Animals; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000378:metabolism*; D001710:Biotin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D016503:Drug Delivery Systems / Q000379:methods*; D006695:Holmium / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000378:metabolism; D007275:Injections, Intravenous; D008187:Lutetium / Q000008:administration & dosage / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011399:Promethium / Q000008:administration & dosage / Q000493:pharmacokinetics; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D019809:Streptavidin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000912:Antibodies, Neoplasm; C091202:B72.3 antibody; C405616:DOTA-biotin; D007128:Immunoglobulin Fragments; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D008187:Lutetium; D001710:Biotin; D019809:Streptavidin; D006695:Holmium; D011399:Promethium