TY - JOUR
T1 - Improved tumor-to-organ ratios of a novel 67Ga-human epidermal growth factor radionuclide conjugate with preadministered antiepidermal growth factor receptor affibody molecules
AU - Sandström, Karl
AU - Haylock, Anna Karin
AU - Velikyan, Irina
AU - Spiegelberg, Diana
AU - Kareem, Heewa
AU - Tolmachev, Vladimir
AU - Lundqvist, Hans
AU - Nestor, Marika
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - The overexpression 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. This study assesses the biodistribution of a novel human epidermal growth factor (hEGF) radionuclide conjugate after preinjection 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 preinjection with one of the anti-EGFR affibody molecules Z EGFR:1907, (Z EGFR:1907) 2, or (Z EGFR: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. Preinjection 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 (Z EGFR:1907) 2 exhibited the best results. These findings show that preblocking with an anti-EGFR affibody molecule is a promising tool that could improve the outcome of radionuclide-based imaging of EGFR-expressing tumors.
AB - The overexpression 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. This study assesses the biodistribution of a novel human epidermal growth factor (hEGF) radionuclide conjugate after preinjection 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 preinjection with one of the anti-EGFR affibody molecules Z EGFR:1907, (Z EGFR:1907) 2, or (Z EGFR: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. Preinjection 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 (Z EGFR:1907) 2 exhibited the best results. These findings show that preblocking with an anti-EGFR affibody molecule is a promising tool that could improve the outcome of radionuclide-based imaging of EGFR-expressing tumors.
KW - affibody molecule
KW - EGFR
KW - gallium
KW - head and neck cancer
KW - molecular imaging
KW - tumor-to-organ ratio
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U2 - 10.1089/cbr.2011.0981
DO - 10.1089/cbr.2011.0981
M3 - Article
C2 - 21834651
AN - SCOPUS:80054709746
VL - 26
SP - 593
EP - 601
JO - Cancer Biotherapy and Radiopharmaceuticals
JF - Cancer Biotherapy and Radiopharmaceuticals
SN - 1084-9785
IS - 5
ER -