Improved Tumor-to-Organ Ratios of a Novel 67Ga-Human Epidermal Growth Factor Radionuclide Conjugate with Preadministered Antiepidermal Growth Factor Receptor Affibody Molecules
2011 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 26, no 5, 593-601 p.Article in journal (Refereed) Published
The over-expression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis. Targeted nuclear imaging of the EGFR expression could improve the diagnostics in patients with HNSCC. However, the high expression of EGFR in normal organs may conceal the tumor uptake and therefore limit the use.
In this study, we have assessed the biodistribution of a novel hEGF radionuclide conjugate after pre-injection with anti-EGFR Affibody molecules. hEGF was conjugated with p-SCN-Bn-NOTA and labeled with 67Ga. The biodistribution of [67Ga]Ga-NOTA-Bn-NCS-hEGF in nude mice with EGFR-expressing xenografts was evaluated either alone or 45 minutes after pre-injection with one of the anti-EGFR Affibody molecules ZEGFR:1907, (ZEGFR:1907)2 or (ZEGFR:955)2.
The novel radioimmunoconjugate, [67Ga]Ga-NOTA-Bn-NCS-hEGF demonstrated high stability in vitro and specific binding to hEGF in vitro and in vivo. Pre-injection with anti-EGFR Affibody molecules improved the tumor-to-organ ratio in the liver, salivary glands and colon. Overall, the dimeric high affinity Affibody molecule (ZEGFR:1907)2 exhibited the best results.
These findings show that pre-blocking with an anti-EGFR Affibody molecule is a promising tool that could improve the outcome of radionuclide-based imaging of EGFR-expressing tumors.
Place, publisher, year, edition, pages
2011. Vol. 26, no 5, 593-601 p.
EGFR, Gallium, Affibody molecule, Head and neck cancer, Molecular imaging, Tumor-to-organ ratio
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-156521DOI: 10.1089/cbr.2011.0981ISI: 000296087300009PubMedID: 21834651OAI: oai:DiVA.org:uu-156521DiVA: diva2:432052