TY - JOUR
T1 - Imaging of HER3-expressing xenografts in mice using a 99mTc(CO) 3-HEHEHE-ZHER3:08699 affibody molecule
AU - Orlova, Anna
AU - Malm, Magdalena
AU - Rosestedt, Maria
AU - Varasteh, Zohreh
AU - Andersson, Ken
AU - Selvaraju, Ram Kumar
AU - Altai, Mohamed
AU - Honarvar, Hadis
AU - Strand, Joanna
AU - Ståhl, Stefan
AU - Tolmachev, Vladimir
AU - Löfblom, John
N1 - Funding Information:
Acknowledgments This work was supported by grants from the Swedish Cancer Society (Cancerfonden) and the Swedish Research Council (Vetenskapsrådet).
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - Purpose: Human epidermal growth factor receptor type 3 (HER3) is a transmembrane receptor tyrosine kinase belonging to the HER (ErbB) receptor family. Membranous expression of HER3 is associated with trastuzumab resistance in breast cancer and the transition to androgen independence in prostate cancer. Imaging of HER3 expression in malignant tumors may provide important diagnostic information that can influence patient management. Affibody molecules with low picomolar affinity to HER3 were recently selected. The aim of this study was to investigate the feasibility of HER3 imaging using radiolabeled Affibody molecules. Methods: A HER3-binding Affibody molecule, Z08699, with a HEHEHE-tag on N-terminus was labeled with 99mTc(CO)3 using an IsoLink kit. In vitro and in vivo binding specificity and the cellular processing of the labeled binder were evaluated. Biodistribution of 99mTc(CO)3-HEHEHE-Z08699 was studied over time in mice bearing HER3-expressing xenografts. Results: HEHEHE-Z08699 was labeled with 99mTc(CO)3 with an isolated yield of >80 % and a purity of >99 %. Binding of 99mTc(CO) 3-HEHEHE-Z08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of the receptor/Affibody molecule complex (70 % of cell-associated radioactivity was internalized after 24 h). The tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor-mediated uptake was also found in the liver, lung, stomach, intestine, and salivary glands. At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions: The results of this study suggest the feasibility of HER3-imaging in malignant tumors using Affibody molecules.
AB - Purpose: Human epidermal growth factor receptor type 3 (HER3) is a transmembrane receptor tyrosine kinase belonging to the HER (ErbB) receptor family. Membranous expression of HER3 is associated with trastuzumab resistance in breast cancer and the transition to androgen independence in prostate cancer. Imaging of HER3 expression in malignant tumors may provide important diagnostic information that can influence patient management. Affibody molecules with low picomolar affinity to HER3 were recently selected. The aim of this study was to investigate the feasibility of HER3 imaging using radiolabeled Affibody molecules. Methods: A HER3-binding Affibody molecule, Z08699, with a HEHEHE-tag on N-terminus was labeled with 99mTc(CO)3 using an IsoLink kit. In vitro and in vivo binding specificity and the cellular processing of the labeled binder were evaluated. Biodistribution of 99mTc(CO)3-HEHEHE-Z08699 was studied over time in mice bearing HER3-expressing xenografts. Results: HEHEHE-Z08699 was labeled with 99mTc(CO)3 with an isolated yield of >80 % and a purity of >99 %. Binding of 99mTc(CO) 3-HEHEHE-Z08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of the receptor/Affibody molecule complex (70 % of cell-associated radioactivity was internalized after 24 h). The tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor-mediated uptake was also found in the liver, lung, stomach, intestine, and salivary glands. At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions: The results of this study suggest the feasibility of HER3-imaging in malignant tumors using Affibody molecules.
KW - Affibody molecule
KW - HER3
KW - Molecular imaging
KW - Molecular targeting
KW - Technetium-99 m
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U2 - 10.1007/s00259-014-2733-7
DO - 10.1007/s00259-014-2733-7
M3 - Article
C2 - 24622956
AN - SCOPUS:84903722742
VL - 41
SP - 1450
EP - 1459
JO - European Journal of Nuclear Medicine and Molecular Imaging
JF - European Journal of Nuclear Medicine and Molecular Imaging
SN - 1619-7070
IS - 7
ER -