Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers.

Background: 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.

Methods: Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA.

Bispecific antibody complex pre-targeting and targeted delivery of polymer drug conjugates for imaging and therapy in dual human mammary cancer xenografts: targeted polymer drug conjugates for cancer diagnosis and therapy.

Introduction: Doxorubicin, a frontline chemotherapeutic agent, limited by its cardiotoxicity and other tissue toxicities, was conjugated to N-terminal DTPA-modified polyglutamic acid (D-Dox-PGA) to produce polymer pro-drug conjugates. D-Dox-PGA or Tc-99 m labeled DTPA-succinyl-polylysine polymers (DSPL) were targeted to HER2-positive human mammary carcinoma (BT-474) in a double xenografted SCID mouse model also hosting HER2-negative human mammary carcinoma (BT-20).

Methods: After pretargeting with bispecific anti-HER2-affibody-anti-DTPA-Fab complexes (BAAC), anti-DTPA-Fab or only phosphate buffered saline, D-Dox-PGA or Tc-99 m DSPL were administered.

In vitro demonstration of enhanced prostate cancer toxicity: pretargeting with Bombesin bispecific complexes and targeting with polymer-drug-conjugates.

Background: Bombesin has been used to target Bombesin receptor, a growth receptor, which is over-expressed in many cancers, including prostate cancer. Polymer-anti-neoplastic-drug-conjugates (PDC) were also developed to reduce non-specific toxicity and increase tumor toxicity utilizing the enhanced permeability and retention effect, benefitting treatment of large tumors with well-established vasculature.

Purpose: If PDCs were delivered by targeted delivery to cancer cells, tumor toxicity would be enhanced and non-specific toxicity decreased.

Imaging small human prostate cancer xenografts after pretargeting with bispecific bombesin-antibody complexes and targeting with high specific radioactivity labeled polymer-drug conjugates.

Purpose: Pretargeting with bispecific monoclonal antibodies (bsMAb) for tumor imaging was developed to enhance target to background activity ratios. Visualization of tumors was achieved by the delivery of mono- and divalent radiolabeled haptens. To improve the ability to image tumors with bsMAb, we have combined the pretargeting approach with targeting of high specific activity radiotracer labeled negatively charged polymers.

Bispecific antibody complex pre-targeted delivery of polymer-drug conjugates for cancer therapy.

The pretargeting approach using bispecific affibody-antibody complex (BAAC) and targeting of chemotherapeutic drug loaded polymers have been used in breast cancer cell cultures to demonstrate targeted chemotherapy and reduce toxicity to non-pretargeted cancer and cardiac cells. HER2/neu-positive BT-474 and -negative BT-20 human mammary carcinoma cell lines were pretargeted with BAAC and targeted with multi-doxorubicin (Dox) loaded polyglutamic acid (PGA) site specifically modified with diethylene triamine pentaacetic acid (DTPA) (D-Dox-PGA) at the N-terminal of PGA. Toxicity to embryonic cardiocytes and human mammary carcinoma cells were assessed.

Pretargeted gamma imaging of murine metastatic melanoma lung lesions with bispecific antibody and radiolabeled polymer drug conjugates.

Introduction: Bispecific monoclonal antibodies (bsMAbs) have been developed as a pretargeting tool to reduce background activity, thereby increasing target to background (T : B) ratios. To enhance visualization of small lesions in vivo, we have used the pretargeting approach of bsMAb and negatively charged polymers radiolabeled with high-specific radioactivity.

Methods: Imaging of metastatic melanoma lesions localized in lung tissues pretargeted with bsMAb and targeted with high-specific radioactivity polymers was carried out.

Palmitoyl ascorbate liposomes and free ascorbic acid: comparison of anticancer therapeutic effects upon parenteral administration.

Purpose: To evaluate and compare anticancer therapeutic effect of palmitoyl ascorbate liposomes (PAL) and free ascorbic acid (AA).

Methods: Liposomes incorporating palmitoyl ascorbate (PA) were prepared and evaluated for PA content by HPLC. To elucidate mechanism of action of cell death in vitro, effect of various H(2)O(2) scavengers and metal chelators on PA-mediated cytotoxicity was studied.