Radiolabeling and Imaging of 212Pb-TCMC-Trastuzumab

September 11, 2010

Radiolabeling and Imaging of 212Pb-TCMC-Trastuzumab

World Molecular Imaging Congress

September 2010

Michael T. Azure1, Hyunki Kim1, Sui Shen2, Daniel R. Yoder1, Richard M. Machado3, Gilbert Andreoletti4, Patrick L. Maquaire4, Martin Brechbiel5, Kwamena E. Baidoo5, Diane Milenic5, Kurt R. Zinn1, 1Radiology, University of Alabama/Birmingham, Birmingham, AL, USA; 2Radiation Oncology, University of Alabama/Birmingham, Birmingham, AL, USA; 3Engineering, Canberra AREVA, Grand Rapids, MI, USA; 4Chemistry, AREVA NC, Beaumont Hague, France; 5Radiation Oncology, NIH, Bethesda, MD, USA. Contact e-mail:


The potential of 212Pb-TCMC-Trastuzumab as a radiotherapeutic agent was previously reported using the bifunctional chelator TCMC (1,4,7,10-Tetra-(2-Carbamoyl Methyl)-Cyclododecane {Cancer Biother Radiopharm 2005; 20:557}. The dual β- and α particle emanations provide a targeted radiotherapeutic agent with short range and long-range cell destruction. Imaging 212Pb would be advantageous for planned human studies, but thought to be impossible due to the multitude of γ rays and bremsstrahlung associated with the various radioisotopes in the decay of 212Pb. The goal of our research was to image 212Pb with planar (Picker Axis, Philips) and μSPECT/CT (X-SPECT, GammaMedica) imaging. High quality 212Pb eluate (confirmed by HpGe detector) was collected from a 224Ra/212Pb generator (AREVA Med LLC) for all experiments. Trastuzumab was radiolabeled with 212Pb using TCMC, with the final product composition evaluated by HPLC, gel electrophoresis, ITLC, and Scatchard analyses with purified HER2. Phantom studies were conducted with 212Pb using medium energy collimators optimized for the 238 keV emission. Post acquisition phantom and NHP images were enhanced utilizing a planar standard-spatial filter. Imaging studies were conducted after i.p. injection of 212Pb-TCMC- Trastuzumab in mice and a male cynomolgus primate. Imaging includes planar and μSPECT and with a specially collimated portable HpGe (AREVA Canberra) detector for medium to high energy resolution. Qualitative discernable phantom images were obtained from the phantom studies. The 212Pb-TCMC- Trastuzumab was high purity (>95%) with specific and high affinity binding to HER2 receptors. μSPECT studies in mice with medium energy collimators produced excellent images, showing the 212Pb remained in the peritoneal cavity. A peritoneal distribution was also found for the primate at t0h, t4h, t8h, t24h and t48h. The HpGe detector detected multiple gamma ray emissions, including 212Pb and 212Bi. These data indicate that the 212Pb remained in the peritoneal cavity for up to 48h indicating low probability of dissociation of the 212Pb from the antibody. The imaging methods can easily be applied in the planned clinical studies.

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