title: The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia.
abstract: Disease recurrence remains a major limitation to the use of marrow transplantation to treat leukemia. Previous transplant studies have demonstrated that higher doses of total-body irradiation result in less disease recurrence, but more toxicity. In this study, the possibility of delivering radiotherapy specifically to marrow using a radiolabeled anti-CD33 antibody (p67) was explored. Biodistribution studies were performed in nine patients using .05-.5 mg/kg p67 trace-labeled with 131I. In most patients initial specific uptake of 131I-p67 in the marrow was seen, but the half-life of the radiolabel in the marrow space was relatively brief, ranging from 9-41 hr, presumably due to modulation of the 131I-p67-CD33 complex with subsequent digestion and release of 131I from the marrow space. In four of nine patients these biodistribution studies demonstrated that with 131I-p67 marrow and spleen would receive more radiation than any normal nonhematopoietic organ, and therefore these four patients were treated with 110-330 mCi 131I conjugated to p67 followed by a standard transplant regimen of cyclophosphamide plus 12 Gy TBI. All four patients tolerated the procedure well and three of the four are alive in remission 195-477 days posttransplant. This study demonstrates the feasibility of using a radiolabeled antimyeloid antibody as part of a marrow transplant preparative regimen and also highlights a major limitation of using conventionally labeled anti-CD33--namely, the short residence time in marrow. Strategies to overcome this limitation include the use of alternative labeling techniques or the selection of cell surface stable antigens as targets.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: D C
authors.initials: DC
authors.lastname: Matthews
authors.forename: J F
authors.initials: JF
authors.lastname: Eary
authors.forename: C C
authors.initials: CC
authors.lastname: Badger
authors.forename: M
authors.initials: M
authors.lastname: Kellogg
authors.forename: O W
authors.initials: OW
authors.lastname: Press
authors.forename: P J
authors.initials: PJ
authors.lastname: Martin
authors.forename: D R
authors.initials: DR
authors.lastname: Fisher
authors.forename: W B
authors.initials: WB
authors.lastname: Nelp
authors.forename: E D
authors.initials: ED
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D001853:Bone Marrow / Q000528:radiation effects*; D016026:Bone Marrow Transplantation; D005260:Female; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D063268:Sialic Acid Binding Ig-like Lectin 3; D013997:Time Factors
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D007457:Iodine Radioisotopes; D063268:Sialic Acid Binding Ig-like Lectin 3