Affibody-mediated imaging of EGFR expression in prostate cancer using radiocobalt-labeled DOTA-ZEGFR:2377

Bogdan Mitran, Ken Gösta Andersson, Elin Lindström, Javad Garousi, Maria Rosestedt, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova, John Löfblom

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The epidermal growth factor receptor (EGFR) is often overexpressed during prostate cancer (PCa) progression towards androgen-independence after hormone therapy, but the overexpression is lower than in other types of cancers. Despite the low expression, EGFR has emerged as a promising therapeutic target for patients with castration-resistant PCa. Non-invasive methods for determination of EGFR expression in PCa can serve for patient stratification and therapy response monitoring. Radionuclide imaging probes based on affibody molecules (7 kDa) provide high contrast imaging of cancer-associated molecular targets. We hypothesized that the anti-EGFR affibody molecule DOTA-Z EGFR:2377 labeled with 55 Co (positron-emitter, T1/2=17.5 h) would enable imaging of EGFR expression in PCa xenografts. The human PCa cell line DU-145 was used for in vitro and in vivo experiments and 57 Co was used as a surrogate for 55 Co in the present study. Binding of 57 Co-DOTA-Z EGFR:2377 to EGFR-expressing xenografts was saturable with anti-EGFR monoclonal antibody cetuximab, which would motivate the use of this tracer for monitoring the receptor occupancy during treatment. A significant dose-dependent difference in radioactivity accumulation in tumors and normal organs was observed when the biodistribution was studied 3 h after the injection of 10 and 35 μg of 57 Co-DOTA-Z EGFR:2377 : At lower doses the tumor uptake was 2-fold higher although tumor-to-organ ratios were not altered. For clinically relevant organs for PCa, tumor-to-organ ratios increased with time, and at 24 h pi were 2.2±0.5 for colon, 7±2 for muscle, and 4.0±0.7 for bones. Small animal SPECT/CT images confirmed the capacity of radiocobalt labeled DOTA-Z EGFR:2377 to visualize EGFR expression in PCa. In conclusion, the present study demonstrated the feasibility of using the radiocobalt labeled anti-EGFR affibody conjugate Z EGFR:2377 as an imaging agent for in vivo visualization of low EGFR-expressing tumors, like PCa, and for monitoring of receptor occupancy during cetuximab therapy as well as the importance of optimal dosing in order to achieve higher sensitivity molecular imaging.

Original languageEnglish
Pages (from-to)534-542
Number of pages9
JournalOncology Reports
Volume41
Issue number1
DOIs
Publication statusPublished - Jan 2019
Externally publishedYes

Keywords

  • Affibody molecule
  • Cobalt
  • EGFR
  • HER1
  • Molecular imaging
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Affibody-mediated imaging of EGFR expression in prostate cancer using radiocobalt-labeled DOTA-ZEGFR:2377'. Together they form a unique fingerprint.

Cite this