(99m)Tc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors.

(99m)Tc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors. Research Abstract Details 

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(99m)Tc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors. Abstract Text:

Thuy Tran,Torun Engfeldt,Anna Orlova,Mattias ,Joachim Feldwisch,Lars ,Anders Wennborg,Vladimir Tolmachev,Amelie Eriksson ,Thuy Tran,Torun Engfeldt,Anna Orlova,Mattias ,Joachim Feldwisch,Lars ,Anders Wennborg,Vladimir Tolmachev,Amelie Eriksson ,Thuy Tran,Torun Engfeldt,Anna Orlova,Mattias ,Joachim Feldwisch,Lars ,Anders Wennborg,Vladimir Tolmachev,Amelie Eriksson ,

Detection of HER2-overexpression in tumors and metastases is important for the selection of patients who will benefit from trastuzumab treatment. Earlier investigations showed successful imaging of HER2-positive tumors in patients using indium- or gallium-labeled Affibody molecules. The goal of this study was to evaluate the use of (99m)Tc-labeled Affibody molecules for the detection of HER2 expression. The Affibody molecule Z HER2:342 with the chelator sequences mercaptoacetyl-Gly-Glu-Gly (maGEG) and mercaptoacetyl-Glu-Glu-Glu (maEEE) was synthesized by peptide synthesis and labeled with technetium-99m. Binding specificity, cellular retention, and in vitro stability were investigated. The biodistribution of (99m)Tc-maGEG-Z HER2:342 and (99m)Tc-maEEE-Z HER2:342 was compared with (99m)Tc-maGGG-Z HER2:342 in normal mice, and the tumor targeting properties of (99m)Tc-maEEE-Z HER2:342 were determined in SKOV-3 xenografted nude mice. The results showed that the Affibody molecules were efficiently labeled with technetium-99m. The labeled conjugates were highly stable in vitro with preserved HER2-binding capacity. The use of glutamic acid in the chelator sequences for (99m)Tc-labeling of Z HER2:342 reduced the hepatobiliary excretion 3-fold with a single Gly-to-Glu substitution and 10-fold with three Gly-to-Glu substitutions. (99m)Tc-maEEE-Z HER2:342 showed a receptor-specific tumor uptake of 7.9 +/- 1.0 %IA/g and a tumor-to-blood ratio of 38 at 4 h pi. Gamma-camera imaging with (99m)Tc-maEEE-Z HER2:342 could detect HER2-expressing tumors in xenografts already at 1 h pi. It was concluded that peptide synthesis for the coupling of chelator sequences to Affibody molecules for (99m)Tc labeling is an efficient way to modify the in vivo kinetics. Increased hydrophilicity, combined with improved stability of the mercaptoacetyl-triglutamyl chelator, resulted in favorable biodistribution, making (99m)Tc-maEEE-Z HER2:342 a promising tracer for clinical imaging of HER2 overexpression in tumors.

(99m)Tc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors. Publishing Authors By Initials

T Tran,T Engfeldt,A Orlova,M ,J Feldwisch,L ,A Wennborg,V Tolmachev,AE ,T Tran,T Engfeldt,A Orlova,M ,J Feldwisch,L ,A Wennborg,V Tolmachev,AE ,T Tran,T Engfeldt,A Orlova,M ,J Feldwisch,L ,A Wennborg,V Tolmachev,AE ,

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(99m)Tc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioconjugate chemistry

VOLUME: 18

Page Numbers: 1956-64

Journal Abbreviation: Bioconjug. Chem.

ISSN: 1043-1802

DAY: 19

MONTH: 10

YEAR: 2007

(99m)Tc-maEEE-ZHER2:342, an Affibody Molecule-Based Tracer for the Detection of HER2 Expression in Malignant Tumors. Information

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LANGUAGE: eng

NlmUniqueID: 9010319

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AFFILIATION: amelie@biotech.kth.se.

Country: United States

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MEDLINETA: Bioconjug Chem

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