title: Comparative biodistributions of pretargeted radioimmunoconjugates targeting CD20, CD22, and DR molecules on human B-cell lymphomas.
abstract: Pretargeted radioimmunotherapy (PRIT) using streptavidin (SA)-conjugated antibodies (Abs), followed by clearing agent and radiolabeled biotin is a promising method that can increase the effectiveness of RIT, while decreasing the toxicities associated with directly labeled Abs. Although CD20 has been the traditional target antigen for RIT of non-Hodgkin lymphoma (NHL), studies targeting HLA DR and CD22 have yielded promising results. Targeting all 3 antigens at once may further augment the effect of PRIT. This study compares the targeting of Ramos, Raji, and FL-18 lymphoma xenografts with either anti-CD20 Ab/SA (1F5/SA), anti-HLA DR Ab/SA (Lym-1/SA), anti-CD22 Ab/SA (HD39/SA), or all 3 conjugates in combination, followed 24 hours later by a biotin-N-acetyl-galactosamine clearing agent, and 3 hours after that by (111)In-DOTA-biotin. The Ab/SA conjugate yielding the best tumor uptake and tumor-to-normal organ ratios of radioactivity varied depending on the target antigen expression on the cell line used, with 1F5/SA and Lym-1/SA yielding the most promising results overall. Also, the best tumor-to-normal organ ratios of absorbed radioactivity were obtained using single conjugates optimized for target tumor antigen expression rather than the combination therapy. This study highlights the importance of screening the antigenic expression on lymphomas to select the optimal reagent for PRIT.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Pantelias
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Nathan
authors.initials: N
authors.lastname: Hedin
authors.forename: Laura
authors.initials: L
authors.lastname: Saganic
authors.forename: Shani
authors.initials: S
authors.lastname: Wilbur
authors.forename: Donald K
authors.initials: DK
authors.lastname: Hamlin
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.forename: Yukang
authors.initials: Y
authors.lastname: Lin
authors.forename: Diane
authors.initials: D
authors.lastname: Stone
authors.forename: Don
authors.initials: D
authors.lastname: Axworthy
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016499:Radioimmunotherapy / Q000379:methods*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000096:biosynthesis*; D019809:Streptavidin / Q000737:chemistry
chemical_list: D018951:Antigens, CD20; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D051918:Sialic Acid Binding Ig-like Lectin 2; D019809:Streptavidin