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⁹⁰Y-DOTA-hLL2: An Agent for Radioimmunotherapy of Non-Hodgkin’s Lymphoma

¹ Immunomedics, Incorporated, Morris Plains, New Jersey
² Garden State Cancer Center, Belleville, New Jersey
³ Pacific Northwest National Laboratory, Richland, Washington

View larger version (13K): [in a new window]   FIGURE 1. Chemical structures of chelates discussed in article (top: DTPA type; bottom: DOTA type). When R and X both are hydrogen, either chelate is coupled to mAbs through one of their pendant carboxylic acid groups, leading to unstable yttrium complexes in the case of DTPA-type chelates but stable yttrium complexes in the case of DOTA-type chelates. When R is a backbone-substituted linking group, typically a benzyl isothiocyanate, all carboxyl groups remain free for yttrium binding after mAb conjugation, in turn leading to stable complexes for both chelate types, albeit more stable complexes for DOTA type. X is typically hydrogen (Bz-DTPA) or methyl (Mx-DTPA), with yttrium complexes displaying similar stability profiles when used as hLL2 mAb conjugates.

View larger version (16K): [in a new window]   FIGURE 2. Comparative in vitro stabilities of 90Y-DOTA-, 90Y-Mx-DTPA-, and 90Y-Bz-DTPA-hLL2 conjugates in presence of excess of free DTPA chelate in 1% HSA over nearly 9 d at 37°C. Compressed y-axis covers range only from 80% to 100% of initially bound 90Y remaining bound to hLL2 mAb.

View larger version (16K): [in a new window]   FIGURE 3. Comparative in vitro stabilities of 100 nmol/L amounts of 90Y-DOTA-, 90Y-Mx-DTPA-, and 90Y-Bz-DTPA-hLL2 conjugates in normal human serum over nearly 12 d at 37°C. Compressed y-axis covers range only from 80% to 100% of initially bound 90Y remaining bound to hLL2 mAb.

View larger version (39K): [in a new window]   FIGURE 4. Biodistribution of 88Y-DOTA-hLL2 (A) and 88Y-Bz-DTPA-hLL2 (B), in nude mice bearing Ramos tumors, until 240 h after injection. (C) Uptake of 88Y-Bz-DTPA-hLL2 in bone (first column) and washed bone (second column) versus uptake of 88Y-DOTA-hLL2 over same period in bone (third column) and washed bone (fourth column). Data are in terms of %ID/g of tissue. W.B. = washed bone.