Abstract | INTRODUCTION: 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. Positive therapeutic control mice were injected with Dox alone at maximum tolerated dose (MTD). RESULTS: Only BT-474 lesions were visualized by gamma imaging with Tc-99 m-DSPL; BT-20 lesions were not. Therapeutic efficacy was equivalent in mice pretargeted with BAAC/targeted with D-Dox- PGA to mice treated only with doxorubicin. There was no total body weight (TBW) loss at three times the doxorubicin equivalent MTD with D-Dox- PGA, whereas mice treated with doxorubicin lost 10% of TBW at 2 weeks and 16% after the second MTD injection leading to death of all mice. CONCLUSIONS: Our cancer imaging and pretargeted therapeutic approaches are highly target specific, delivering very high specific activity reagents that may result in the development of a novel theranostic application. HER/2 neu specific affibody-anti- DTPA-Fab bispecific antibody pretargeting of HER2 positive human mammary xenografts enabled exquisite targeting of polymers loaded with radioisotopes for molecular imaging and doxorubicin for effective therapy without the associating non- tumor normal tissue toxicities.
|
Authors | Ban-An Khaw, Keyur S Gada, Vishwesh Patil, Rajiv Panwar, Savitri Mandapati, Arash Hatefi, Stan Majewski, Andrew Weisenberger |
Journal | European journal of nuclear medicine and molecular imaging
(Eur J Nucl Med Mol Imaging)
Vol. 41
Issue 8
Pg. 1603-16
(Aug 2014)
ISSN: 1619-7089 [Electronic] Germany |
PMID | 24643779
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antibodies, Bispecific
- Drug Carriers
- Polyglutamic Acid
- Technetium
- Pentetic Acid
- Doxorubicin
- Receptor, ErbB-2
|
Topics |
- Animals
- Antibodies, Bispecific
(pharmacokinetics, therapeutic use)
- Carcinoma
(diagnostic imaging, radiotherapy)
- Cell Line, Tumor
- Doxorubicin
(chemistry, pharmacokinetics, therapeutic use)
- Drug Carriers
(chemistry)
- Female
- Humans
- Mammary Neoplasms, Experimental
(diagnostic imaging, radiotherapy)
- Mice
- Mice, SCID
- Pentetic Acid
(chemistry)
- Polyglutamic Acid
(chemistry)
- Radioimmunotherapy
- Radionuclide Imaging
- Receptor, ErbB-2
(immunology)
- Technetium
(therapeutic use)
- Tissue Distribution
- Xenograft Model Antitumor Assays
|