The broad long-term objectives of this project are to apply new anti-hapten monoclonal antibodies to PET and SPECT tumor imaging with Ga-68 chelates and Tc-99m pertechnetate. We will apply our novel pretargeting technology using bifunctional monoclonal antibodies with at least one target specific site and one hapten specific site. These non-radioactive conjugates will be injected and allowed to localize. After maximum target accumulation has occurred, blood levels will be rapidly lowered by injection of a suitable chase. This will be quickly followed with an injection of Ga-68 chelate or Tc-99m pertechnetate. Imaging will be carried out 1 to 3 hours following injection of the the radiolabel. For the Ga-68 experiments the use of antibodies specific for the chelates of Ga and having much larger binding constants for Ga chelates than for the other contaminating metal chelates in the generator eluant will make purification unnecessary. This will allow the Ga-68 chelates to be injected soon after elution of the generator and permit the use of small amounts af antibody. For the Tc-99m studies a monoclonal antibody binding the pertechnetate anion with high affinity will be employed in the bifunctional antibody. This will eliminate the need for reduction of pertechnetate with stannous ions, greatly simplifying its use. In addition to pretargeting with anti-Tc-99m04 antibody the 6 hr half- life of Tc-99m is long enough to allow the Tc-Ab complex to be injected, followed by a suitable chase 5 to 6 hrs later and images to be made 1-2 hrs after the chase. The methodology involves immunizing mice with specially designed antigens, screening by whole body counting of mice with radioactive antigens, organ distribution and gamma camera imaging in tumor mice and PET and SPECT images in rabbits bearing VX2 tumor. The ultimate aim is to make PET and SPECT images of tumors in humans with Ga-68 chelates and Tc-99 pertechnetate. These studies will improve tumor to background ratios, reduce patient radiation exposure, enhance the definition of tumors through PET and SPECT imaging, and provide a more accurate method for quantitation of biodistribution in humans using readily available and relatively inexpensive generator produced radionuclides.
