title: Are radiometal-labeled antibodies better than iodine-131-labeled antibodies: comparative pharmacokinetics and dosimetry of copper-67-, iodine-131-, and yttrium-90-labeled Lym-1 antibody in patients with non-Hodgkin's lymphoma.
abstract: Radioimmunotherapy using radiolabeled monoclonal antibodies against tumor-associated antigens has been efficacious, particularly in the treatment of radiosensitive malignancies such as lymphoma. Antilymphoma monoclonal antibody Lym-1, labeled with copper-67 ((67)Cu), iodine-131 ((131)I), or yttrium-90 ((90)Y), has been effective salvage therapy for patients with non-Hodgkin's lymphoma. Although (131)I has had the dominant role in radioimmunotherapy thus far, several properties of radiometals are preferable. A total of 70 patients with B-lymphocytic non-Hodgkin's lymphoma were studied using (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, or (111)In-2IT-BAD-Lym-1. Because (90)Y does not have good emissions for imaging, indium-111 ((111)In), its analogue, was used as a surrogate to estimate (90)Y-2IT-BAD-Lym-1 pharmacokinetics and radiation dosimetry. Subsets of four patients in each group received (67)Cu- and (131)I-labeled Lym-1 or (111)In- and (131)I-labeled Lym-1, allowing direct comparisons of the radioimmunoconjugates. Sequential blood samples and planar images were used to quantitate radioimmunoconjugate in tissues in order to determine pharmacokinetics and radiation dosimetry. (67)Cu-2IT-BAT-Lym-1 and (90)Y-2IT-BAD-Lym-1 exhibited higher cumulated activity concentrations and radiation absorbed doses per unit of administered radioactivity for tumors than did (131)I-Lym-1. The mean tumor cumulated activity (area under the time-activity curve) concentrations per unit of administered radioactivity for (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 96.89, 33.96, and 43.42 GBq-s/GBq/g, respectively. The mean tumor radiation doses from (67)Cu-2IT-BAT-Lym-1, (131)I-Lym-1, and (90)Y-2IT-BAD-Lym-1 were 2.5, 1.0, and 6.6 Gy/GBq, respectively, because (90)Y deposits more radiation per unit of administered radioactivity. Per unit of administered radioactivity, radiation doses from (67)Cu-2IT-BAT-Lym-1 and (131)I-Lym-1 to normal tissues were similar except that the liver received a higher dose from (67)Cu-2IT-BAT-Lym-1 than from (131)I-Lym-1; radiation doses to normal tissues from (90)Y-2IT-BAD-Lym-1 were generally higher. Consequently, the therapeutic indices (ratio of radiation doses to tumor and normal tissues) for (67)Cu-2IT-BAT-Lym-1, and less generally for (90)Y-2IT-BAD-Lym-1, were more favorable when compared to those for (131)I-Lym-1. Data from the matched subsets of patients showed similar therapeutic indices to those for the groups of patients. (67)Cu-2IT-BAT-Lym-1 showed more potential than (131)I-Lym-1 or (90)Y-2IT-BAD-Lym-1 for non-Hodgkin's lymphoma radioimmunotherapy.
authors.affiliation: Division of Hematology/Oncology, Molecular Cancer Institute, Sacramento, CA 95816, USA. gldenardo@ucdavis.edu
authors.forename: G L
authors.initials: GL
authors.lastname: DeNardo
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: R T
authors.initials: RT
authors.lastname: O'Donnell
authors.forename: L A
authors.initials: LA
authors.lastname: Kroger
authors.forename: D L
authors.initials: DL
authors.lastname: Kukis
authors.forename: C F
authors.initials: CF
authors.lastname: Meares
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
authors.forename: S
authors.initials: S
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D003301:Copper Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: C410508:2IT-BAD-Lym-1 monoclonal antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003301:Copper Radioisotopes; D006571:Heterocyclic Compounds; D007457:Iodine Radioisotopes; C410509:Lym-1 monoclonal antibody; D009942:Organometallic Compounds; D015021:Yttrium Radioisotopes; C097568:copper-67-2IT-BAT-Lym-1