Panel Disdussion

3rd International Congress 3rd International of Nuclear Congress Medicine of Nuclear & 15th Medicine Iranian Annual & 15th Iranian Congress Annual of
Nuclear Congress Medicine of Nuclear Medicine
Shahid Beheshti Shahid Beheshti University University of Medical Sciences of Medical 19-21 Sciences May 201119-21 May 2011
Synthesis and biodistribution studies of 67Ga-DOTAtrastuzumab
as a diagnostic radioimmunoconjugate for
oncology imaging by SPECT
Behrooz Alirezapour 1 , Amir Reza Jalilian 1 , Mohammad javad Rasaee 2 ,
Saeed Rajabifar 1 , Kamal Yavari 1 , Javad Mohammadnejad 1 ,
Mohammad Reza Aboudzadeh 1 , Fatemeh Bolourinovin 1 , Sedigheh
Moradkhani 1 , Mojtaba Fathi 2
1 Nuclear Science and Technology Research Institute (NSTRI)
2 Tarbiat Modares University(TMU)
Introduction: Radiolabeled monoclonal antibodies have shown great
promise for cancer diagnosis and therapy. Trastuzumab (trade name;
Herceptin) is a humanized IgG1 monoclonal antibody directed against
the extracellular domain of the Human Epidermal Growth Factor
Receptor 2(HER2). HER 2 receptor is over expressed in 20-30% of
the early-stage breast cancers and these patients may be candidates
for Herceptin treatment. we attempted to label trastuzumab with
radioactive gallium(67Ga) 67Ga is cyclotron produced, decays by
electron capture (EC) with t1/2 = 77.9h accompanied with γ-rays,
mainly 93, 184 and 296 keV, and is suitable for SPECT imaging. In
the present study, 67Ga labeled trastuzumab was prepared followed
by the biodistribution studies in normal mice.
Methods: Herceptin was conjugated with DOTA-NHS-ester
(Macrocyclics), purified by molecular filtration, the average number of
DOTA conjugated per mAb was calculated and total concentration
was determined by spectrophotometrically. DOTA-Trastuzumab was
labeled with 67Ga then Radiochemical purity, integrity of protein after
radiolabeling and stability of 67Ga -DOTA-Trastuzumab were
determined. The biodistribution studies was performed in normal rats
(67Ga -DOTA-Trastuzumab i.v., 75 ± 5.5 µCi, 30min, 2h, 4h, 24h,
48h, 72h).
Result: The radioimmunoconjugate was prepared with a
radiochemical purity of 88% (RTLC). The average chelate to antibody
ratio(c/a) for the conjugate used in this study was 5.8:1. The final
compound was stable in presence of PBS at 37ºC and room
temperature.The sample were showed to have similar patterns of
migration in the gel electrophoresis.The accumulation of the
radiolabeled antibody in lungs, liver, spleen and other tissues
demonstrates a similar pattern to the other radiolabeled anti-HER2
immunoconjugates.
Conclusion: 67Ga-DOTA-Trastuzumab is potentially good probe for
diagnosis and treatment studies of HER2 expression in oncology by
SPECT.
Keywords: 67Ga DOTA, Radioimmunoconjugate, Trastuzumab,
HER2
142