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Snyder Lab: Research

Copper-64 labeled Antibody to Image GD2 Expression

Several monoclonal antibodies targeting disialoganglioside GD2 have been investigated in clinical trials for treating neuroblastoma, a pediatric tumor derived from primordial neural crest cells.  One of these antibodies, hu14.18K322A, contains a single, point mutation shown to decrease complement activation with the attempt to minimize dose-limiting side effects.  A phase I clinical trial using this antibody is being conducted at our institution.   Our objective is to radiolabel this antibody with 64Cu, a positron-emitting nuclide with a 12.7 hour half-life, enabling PET imaging at the late time-points needed for antibody localization.  Such an imaging moiety would be useful in following response to therapy or possibly in identifying potential responders prior to initiation of treatment.

Fluorine-18 Labeling of Substituted Benzils for Imaging Carboxylesterase

Irinotecan is a potent chemotherapeutic used in the treatment of several cancers, including neuroblastoma. Irinotecan itself is a non-toxic prodrug which is converted in vivo to the cytotoxic form via metabolism by carboxylesterase (CE) enzymes. Researchers at St. Jude Children's Research Hospital are taking advantage of CE isoform diversity to design a two-pronged protocol of tumor specific chemotherapy. These complementary approaches combine specific inhibition of human CE activity in normal tissues in an effort to increase drug delivery to the tumor, and tumor-specific activation of prodrugs by using neural progenitor cells transfected with a carboxylesterase cDNA. The tumor-selective trafficking of neural progenitor cells allows over expression of CE within the tumor.  Both lines of investigation would benefit from in vivo quantification of CE activity in tumors and normal tissues, allowing titration of drug dosing for CE inhibitors and measurement of CE increases selectively at tumor foci in progenitor cell studies. Our laboratory is developing PET radiotracers based on CE inhibitors developed here at St Jude, many of which contain a benzil (diphenylethane-1,2-dione) core structure. 

Nanoparticle-Antibody delivery agents

Synthetic magnetic nanoparticles (MNP's) are versatile probes suitable for various biomedical applications, ranging from in vitro sensors for the detection of genetic or other molecular abnormalities to in vivo delivery systems for a variety of diagnostic and therapeutic agents. Super-paramagnetic nanoparticles are sensitive probes for MRI-based molecular imaging. Their chemical properties allow for the conjugation with other biological units such as antibodies for specific molecular targeting. Our group is interested in the development of "all-in-one" nanoparticle probes for simultaneous multimodal imaging, drug delivery and other theranostic applications.