(450b) Development of Zr-89 PET Radiopharmaceuticals for Cancer Imaging

The use of Positron Emission Tomography (PET) for cancer imaging is a well-established and widely used molecular imaging modality both in clinical and research settings. PET offers the ability to quantitatively measure biological and receptor-based processes using a wide spectrum of specifically designed radiopharmaceuticals. The use of PET is expanding and the inclusion of longer-lived radiometal positron-emitters is broadening the application and appeal of this imaging modality.

Zr-89 has emerged as a promising radionuclide for use in immunoPET. Zirconium-89 has a number of distinct advantages which make it ideal for immunoPET: (i) the radioactive half-life of 78.41 h matches closely the extend times required for optimum biodistribution of intact mAbs, (ii) the positron yield of 22.7% is comparable to that of Cu-64, Y-86 and I-124 which improves counting statistics in PET imaging, (iii) zirconium and its ions are generally inert to biological systems and have no known biological role or function, (iv) cyclotron production of Zr-89 via the (p,n) transmutation reaction using a 100% naturally abundant Y-89 solid target is highly efficient and cost effective, and (v) high purity and high specific-activity Zr-89 is now available in various chemical forms which are suitable for radiolabeling mAbs.

This presentation will review the current state-of-the-art in non-standard PET nuclide application with an emphasis on the use of radiometals (e.g., Zr-89) with peptide and antibody constructs. In addition, since the effective use of a radiometal nuclide often relies on their attachment to the targeting probe via a bifunctional chelator, this talk will focus on novel strategies for using “click” chemistry methodology for attachment of the radiometals to active biomolecules.