title: A comparison of the biodistribution and biokinetics of (99m)Tc-anti-CD66 mAb BW 250/183 and (99m)Tc-anti-CD45 mAb YTH 24.5 with regard to suitability for myeloablative radioimmunotherapy.
abstract: Radioimmunotherapy (RIT) with radiolabelled monoclonal antibodies (mAbs) is an effective method of achieving myeloablation in leukaemia patients prior to stem cell transplantation (SCT). We wished to compare the approaches of specific binding to leukaemic blasts and non-specific binding to benign red marrow cells, which results in a myeloablative "cross-fire" effect. Therefore, we prospectively evaluated the biodistribution and biokinetics of the anti-CD45 mAb YTH 24.5 and the anti-CD66 mAb BW 250/183 with regard to their suitability for myeloablative RIT. The red marrow selective anti-CD66 mAb BW 250/183 (IgG1) binds to normal granulopoietic cells. In contrast, the anti-CD45 mAb YTH 24.5 (IgG2b) binds to 85-90% of acute leukaemic blasts and almost all haematopoietic white cells. Patients with leukaemic blast infiltration of the marrow <25% and assigned for RIT and SCT were included. Twelve patients (eight male, four female; median age 46+/-7 years) with AML (5), CML (5) or ALL (2) were examined. Both mAbs were labelled with technetium-99m. Within 48 h, 906+/-209 MBq (99m)Tc-anti-CD66 mAb and 760+/-331 MBq (99m)Tc-anti-CD45 mAb were injected consecutively. Scintigraphic and urinary measurements were performed 1, 2, 4 and 24 h after injection. Serum activities were evaluated 2, 5, 10, 15, 30 and 60 min and 2, 4 and 24 h after injection. Compared with the anti-CD45 mAb, the anti-CD66 mAb showed an approximately fourfold higher accumulation in the red marrow, a 2.5-fold lower accumulation in the liver and similar accumulation in the kidneys. The serum activity (% of the injected dose) initially decreased faster for the anti-CD45 mAb but was similar for the two mAbs 24 h after injection: 3.3%+/-1.2% (anti-CD66 mAb) and 2.4%+/-1.1% (anti-CD45 mAb). The cumulated urinary excretion was 17%+/-6.6% (anti-CD66 mAb) and 27.3%+/-7.9% (anti-CD45 mAb) 24 h after application. In these patients with low tumour load, the anti-CD66 mAb BW 250/183 showed more favourable properties in terms of biodistribution and pharmacokinetics. Thus, it appears superior to anti-CD45 mAb YTH 24.5 in selectively increasing the marrow dose and avoiding extramedullary organ toxicity.
authors.affiliation: Department of Nuclear Medicine, University Hospital, Ulm, Germany, buchmann@nuklear.klinik.uni-mainz.de
authors.forename: Inga
authors.initials: I
authors.lastname: Buchmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Kull
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hale
authors.forename: Jorg
authors.initials: J
authors.lastname: Kotzerke
authors.forename: Dirk
authors.initials: D
authors.lastname: Rattat
authors.forename: Hartmut
authors.initials: H
authors.lastname: Dohner
authors.forename: Sven N
authors.initials: SN
authors.lastname: Reske
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D001853:Bone Marrow / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000532:radiotherapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine; D014018:Tissue Distribution; D014915:Whole-Body Counting / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D019653:Myeloablative Agonists; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals