imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-dtpa antibody and tc-99m-labeled polymers

Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. however, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-dtpa-fab-fab’ and targeting with high-specific radioactivity tc-99m-dtpa-succinylated-polylysine (dspl) was developed. mice were injected biweekly with 10 mg/kg dox or its equivalent as d-dox-pga. tc-99m-dspl myocardial activity after pretargeting with bsab-fab-fab’ was determined after gamma imaging performed at day 7 for dox-treated mice and day 39 for all others. mice treated with 10 mg/kg dox lost 10% total body weight in 1 week and 20% after a second dose. pretargeted mice treated with 30 mg/kg cumulative d-dox-pga dose showed no loss of body weight for the duration of the study. cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% id/g ± sd]) after 1 dose of dox. mice injected with 3 × 10 mg/kg dox equivalent as d-dox-pga (0.4 ± 0.04, p < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, p < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg dox group. pretargeting with bsab-fab-fab’ and targeting with tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. tolerated dose of d-dox-pga was greater than to 30 mg/kg dox-equivalent dose with minimal cardiotoxicity.