TY - JOUR
T1 - Kit formulation for 99mTc-labeling of recombinant anti-HER2 Affibody molecules with a C-terminally engineered cysteine
AU - Ahlgren, Sara
AU - Andersson, Kristofer
AU - Tolmachev, Vladimir
N1 - Funding Information:
This work was financially supported by the Swedish Cancer Society (Cancerfonden) and the Swedish Research Council (Vetenskapsrådet) as well as Nils and Märta Schuberts Foundation. The authors would like to thank Dr. Anna Orlova for experimental help and Dr. Lars Abrahmsén for feedback on the manuscript.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/7
Y1 - 2010/7
N2 - Introduction: Molecular imaging of human epidermal growth factor receptor type 2 (HER2)-expression in malignant tumors provides potentially important information for patient management. Affibody molecules have shown to be suitable tracers for imaging applications using single photon emission computed tomography or positron emission tomography. Results from an earlier evaluation of the application of site-specific 99mTc-labeling of the Affibody molecule, ZHER2:2395-C, were favorable. Methods: As a preparation for clinical application of this tracer, we have developed and evaluated a robust single-vial freeze-dried kit, allowing labeling of the Affibody molecule, ZHER2:2395-C, with 99mTc. Results: The composition of the kit [containing glucoheptonate, EDTA and tin(II)-chloride], as well as the protein amount and the pertechnetate volume were optimized for a high labeling yield (>90%) and minimal presence of reduced hydrolyzed technetium colloids (<1%). The specificity to HER2 receptors, the binding competence and the stability in phosphate-buffered saline and murine serum were verified in vitro. The shelf-life was also evaluated in vitro. , showing no reduction in labeling yield or binding capacity to HER2-expressing cells after over 400 days of storage of the single-vial freeze-dried kit. Conclusions: ZHER2:2395-C labeled with 99mTc using the lyophilized kit was stable and resulted in a favorable biodistribution in an in vivo evaluation in normal Naval Medical Research Institute mice.
AB - Introduction: Molecular imaging of human epidermal growth factor receptor type 2 (HER2)-expression in malignant tumors provides potentially important information for patient management. Affibody molecules have shown to be suitable tracers for imaging applications using single photon emission computed tomography or positron emission tomography. Results from an earlier evaluation of the application of site-specific 99mTc-labeling of the Affibody molecule, ZHER2:2395-C, were favorable. Methods: As a preparation for clinical application of this tracer, we have developed and evaluated a robust single-vial freeze-dried kit, allowing labeling of the Affibody molecule, ZHER2:2395-C, with 99mTc. Results: The composition of the kit [containing glucoheptonate, EDTA and tin(II)-chloride], as well as the protein amount and the pertechnetate volume were optimized for a high labeling yield (>90%) and minimal presence of reduced hydrolyzed technetium colloids (<1%). The specificity to HER2 receptors, the binding competence and the stability in phosphate-buffered saline and murine serum were verified in vitro. The shelf-life was also evaluated in vitro. , showing no reduction in labeling yield or binding capacity to HER2-expressing cells after over 400 days of storage of the single-vial freeze-dried kit. Conclusions: ZHER2:2395-C labeled with 99mTc using the lyophilized kit was stable and resulted in a favorable biodistribution in an in vivo evaluation in normal Naval Medical Research Institute mice.
KW - Affibody molecules
KW - Freeze drying/lyophilization
KW - HER2
KW - Imaging
KW - Kit-formulation
KW - Technetium
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U2 - 10.1016/j.nucmedbio.2010.02.009
DO - 10.1016/j.nucmedbio.2010.02.009
M3 - Article
C2 - 20610158
AN - SCOPUS:77953872478
VL - 37
SP - 539
EP - 546
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
SN - 0969-8051
IS - 5
ER -