Comparative biodistribution of imaging agents for in vivo molecular profiling of disseminated prostate cancer in mice bearing prostate cancer xenografts: focus on 111In- and 125I-labeled anti-HER2 humanized monoclonal trastuzumab and ABY-025 affibody.

Abstract

INTRODUCTION:

Human epidermal growth factor receptor type 2 (HER2) overexpression supports proliferation of androgen-independent prostate cancer (PC). Radionuclide molecular imaging of HER2 expression in disseminated PC would aid in the selection of patients who are likely responders to HER2 targeting therapy. In this study, we evaluated whether ABY-025 Affibody molecule, a small (∼ 7-kDa) HER2-binding scaffold protein, produces superior tumor-to-nontumor ratios compared with those obtained through the use of radiolabeled humanized anti-HER2 antibody, trastuzumab. The influence of (111)In vs. (125)I radiolabel was evaluated for both tracers.

METHODS:

ABY-025 was labeled with (111)In using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelator, site-specifically coupled to the C-terminus via the maleimido derivative. Trastuzumab was labeled with (111)In using a CHX-A″ diethylene triamine pentaacetic acid (DTPA) chelator. An indirect radioiodination with [(125)I]-N-succinimidyl-para-iodobenzoate was used for both targeting proteins. Biodistribution of all labeled targeting proteins was evaluated in mice bearing DU-145 PC xenografts.

RESULTS:

The use of residualizing (111)In-label facilitated better tumor uptake and better tumor-to-nontumor ratios for both targeting agents. [(111)In]-ABY-025 provided tumor uptake of 7.1±0.8% injected dose per gram of tissue (% ID/g) and tumor-to-blood ratio of 47±13 already at 6 h postinjection. The maximum tumor-to-nontumor ratios with [(111)In]-CHX-DTPA-trastuzumab were achieved at 72 h postinjection, whereas tumor uptake was 11±4% ID/g and tumor-to-blood ratio was 18±7. The biodistribution data were confirmed with gamma-camera imaging.

CONCLUSIONS:

Radiolabeled ABY-025 Affibody molecule provides higher contrast in imaging of HER2-expressing PC xenografts than radiolabeled trastuzumab. Residualizing radiometal label for ABY-025 provides better contrast in imaging of HER2-expressing PC xenografts than nonresidualizing radiohalogen.

• Authors: Jennie Malmberg, Mattias Sandström, Kenneth Wester, Vladimir Tolmachev, Anna Orlova
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 38 Issue 8 Pg. 1093-102 (Nov 2011) ISSN: 1872-9614 [Electronic] United States
• PMID: 22137850 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• ABY-025
• Antibodies, Monoclonal, Humanized
• Indium Radioisotopes
• Iodine Radioisotopes
• Peptide Fragments
• Radiopharmaceuticals
• Staphylococcal Protein A
• Erbb2 protein, mouse
• Receptor, ErbB-2
• Trastuzumab

Topics

• Animals
• Antibodies, Monoclonal, Humanized (pharmacokinetics)
• Indium Radioisotopes (pharmacokinetics)
• Iodine Radioisotopes (pharmacokinetics)
• Male
• Mice
• Mice, Inbred BALB C
• Peptide Fragments (pharmacokinetics)
• Prostatic Neoplasms (diagnostic imaging)
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis)
• Receptor, ErbB-2 (metabolism)
• Staphylococcal Protein A
• Tissue Distribution
• Trastuzumab