Cancer-Specific Positron Emission Tomography Tracer (2009-048)
University of Iowa Research Foundation
Contact
Catherine Koh
catherine-koh@uiowa.edu
319-335-4659
Background
Researchers at the University of Iowa have developed a new cancer-specific radioactive tracer for use in
Positron Emission Tomography (PET). As medical imaging plays an increasing role in the diagnosis and
monitoring of patients, PET has emerged as a promising technology supporting the treatment of cancer and
other diseases. PET has historically been associated with tracking metabolic activity in the body to create its
images (primarily using 18F-fluorodeoxyglucose [18F-FDG]). In practice, however, any positron emitting
substance that can be targeted to a specific area can be used for PET imaging.
By focusing on tracers that target DNA proliferation instead of energy use, it is believed that PET can deliver
improved, more accurate imaging. The tracer 3’-18F-thymidine, for instance, is currently in clinical trials and
can be used to track cancers that overexpress thymidine kinase to scavenge thymine from the blood. A newer
technology developed by researchers at the University of Iowa focuses on the de novo biosynthesis of this
DNA base to offer even greater cancer specificity.
Technology
The invention created by scientists at the University of Iowa is a radioactive tracer compound known to
target cells producing new copies of their DNA in preparation for replication. The compound – [11-11C]
N5,N10-methylene-5,6,7,8-tetrahydrofolate – incorporates a radioactive tag into newly synthesized genomic
DNA molecules during replication. As a marker for PET scans, this tag has the potential to generate images of
cancer growth with lower background and more specificity than is achieved with glucose-based markers.
Researchers have also developed two clinically relevant derivatives of this compound. The first, [11-11C] N5formyl-5,6,7,8-tetrahydrofolate (also known as labeled folinic acid, Leucovoring, or Citrovorum factor) is a
more stable from of the tracer. The second derivative is [11-11C] N5-methyl-5,6,7,8-tetrahydrofolate, which is a
major source for single carbon in protein and DNA methylation.
Advantages
Conducting PET imaging with metabolic tracers can be overly non-specific – accumulating in healthy organs
and offering a low target-to-background ratio. In practice, this can lead to false positive results and/or
underestimate the effectiveness of chemotherapy. It is believed that clinical decision making could be
substantially improved through the use of [11-11C] N5,N10-methylene-5,6,7,8-tetrahydrofolate (and/or its
derivatives), which targets proliferating cell types more specifically and should lead to higher-yield PET
images.
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Non-invasive diagnostic tool that can indicate location of cancerous tumor and its potential response
to chemotherapeutic drugs
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Radioactive tracer for use in PET targets de novo DNA biosynthesis
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Provides increased specificity for proliferating cell types, lower background-to-target ratio
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Nontoxic, natural metabolites that do not affect or alter pathogenesis or healthy tissue
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Potential to improve clinical decision making in context of oncology, nuclear medicine, pre-biopsy
assessment, post-surgical assessment, and chemotherapy response analysis
Relevant Research
Saeed M, Tewson TJ, Erdahl CE, Kohen A. A fast chemo-enzymatic synthesis of [11C]-N5,N10methylenetetrahydrofolate as a potential PET tracer for proliferating cells. Nucl. Med. Biol. Accepted for
publication Dec 2011. www.nucmedbio.com/article/S0969-8051(11)00305-2/abstract.
Saeed M, Sheff D, Kohen A. A novel positron emission tomography tracer distinguishes normal from
cancerous cells. J. Biol. Chem. 2011. 286: 33872–33878. www.ncbi.nlm.nih.gov/pubmed/21832075.
Hong B & Kohen A. Microscale synthesis of isotopically labeled 6R-N5,N10-methylene-5,6,7,8tetrahydrofolate as a cofactor for thymidylate synthase. J Label Compd Radiopharm. 2005. 48: 759-769.
www.ncbi.nlm.nih.gov/pubmed/15081906.
Hooker J, Schonberger M, Schieferstein H, Fowler J. A simple, rapid method for the preparation of
[11C]Formaldehyde. Angew Chem. 2008. 47: 5989-5992. www.ncbi.nlm.nih.gov/pubmed/18604787.
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