Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Ραδιοφαρμακευτική ΧημείαLibrary of the School of Science
Supervisors info:
Γ.Φώσκολος Καθηγητής ΕΚΠΑ (επιβλέπων), Α. Τσοτίνης Καθηγητής ΕΚΠΑ, Π. Μπουζιώτη Ερευνήτρια Β΄ Ε.Κ.Ε.Φ.Ε. ΄΄ Δημόκριτος΄΄ (συνεπιβλέπουσα)
Original Title:
Μοριακή απεικόνιση της αγγειογένεσης με μονοκλωνικό αντίσωμα επισημασμένο με 99mΤεχνήτιο
Translated title:
Molecular imaging VEGF factor with 99mTc-monoclonal antibody
Summary:
Angiogenesis is a vital process in the growth and metastasis of tumors.
Bevacizumab is a humanized monoclonal antibody which binds to VEGF, thus
blocking the biological pathways of VEGF-induced tumor angiogenesis. The aim of
this study is the development, comparison and evaluation of two novel
radiotracer of 99mTc-bevacizumab in the (I) and (V) oxidation states, which
enables noninvasive imaging of VEGF. The native format of the antibody was
labeled with 99mTc(CO)3 in the first case. The labeling of proteins with
technetium(V) is based on its high affinity for free –SH groups. The partial
reduction of the disulfide bonds to produce free sulfhydryl groups (–SH) was
achieved with 2-mercaptoethanol. The immunoreactivity of the thiol-modified
antibody labeled with 99mTc was assessed in these cases. Radiolabeling
efficiency and in vitro stability was also investigated. In vivo
biodistribution studies of 99mTc-bevacizumab and 99mTc-(CO)3-bevacizumab were
performed in nude mice transplanted with MDA MB 231 beast cancer cells
transfected with the VEGF165 variant. Injection of the radiotracer revealed a
time-dependent and specific localization of radiotracers to the tumor tissue.
Excess of bevacizumab co-injection was achieved for specific binding studies.
Finally, imaging studies showed high tumor-to-background contrast for both
radioimmunoconjugate and need further improvement for potential routine
application in radioimmunodiagnosis.
Keywords:
Radioimmunoconjugate, Monoclonal antibody, Technetium, Angiogenesis, Bevacizumab
Number of references:
139
