Cancer Imaging:
[F-18] FLT in tumor proliferation. Dr. Janet Eary, M.D. principal investigator (UAB Radiology)

Cellular proliferation imaging with specific PET agents provides a robust approach to quantifying the growth rate of tumors and assessing their treatment response. [F-18] Fluorothymidine (FLT) has been shown to accumulate in tissues in aif-research-image 2proportion to the level of cell growth. During cellular uptake, FLT is transported across the cell membrane and then phosphorylated by thymidine kinase-1, resulting in intracellular trapping of the radiolabel. Because of the substitution at the 3'-position, FLT is not a substrate for DNA polymerase. Thymidine kinase-1 activity is controlled throughout the cell cycle processes, which forms the basis for relating FLT uptake to cellular proliferation. Although FLT is not incorporated into DNA, its retention in cells is directly related to thymidine kinase activity, which peaks in S-phase and then is destroyed as the cells proceed to division. Tumor uptake of FLT is also influenced by blood flow, which requires a simple PET quantitative imaging analysis method to obtain tissue proliferation rate information separate from tumor blood flow. PET has the ability to image the whole body and yield quantitative regional tissue information on a specific biological process. FLT PET/CT imaging is presently in use at UAB in imaging patients with acute leukemias and brain tumors.

Muzi M, Mankoff, D. A., Grierson, J. R., Wells, J. M., Vesselle, H., Krohn, K. A. Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies. J Nucl Med 2005; 46 (2), 371-80.

Weber G, Nagai M, Natsumeda Y, Ichikawa S, Nakamura H, Eble JN, Jayaram HN, Zhen WN, Paulik E, Hoffman R, et al. Regulation of de novo and salvage pathways in chemotherapy. Adv Enzyme Regul. 1991;31:45-67.

Neurosciences imaging:
[F-18] FPEB in neurologic and psychiatric disorders.  Dr. Robert Kessler, principal investigator (UAB Radiology) 
J Nucl Med. 2014 May 5;55(7):1119-1121.

The metabotropic glutamate receptor subtype 5 (mGluR5) is a type I metabotropic glutamatergic receptor, which is an important modulator of bothN-methyl-D-aspartate and dopamine receptor signaling; it positively modulates N-methyl-D-aspartate receptor function and has complex interactions with dopamine receptor intracellular signaling (1,2). Altered function of the mGluR5 has been implicated in the pathophysiology of several neurologic and psychiatric disorders including Fragile X syndrome (3), Huntington and Parkinson disease (4,5), psychostimulant drug and alcohol abuse (6–8), depression, and anxiety as well as being involved in learning and memory (9–12). 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) is a promising radioligand for imaging the mGluR5 in humans. It has a high affinity (0.11–0.15 nM) for the mGluR5 and nearly optimal lipophilicity for imaging, with a logP of 2.8 (13). Initial human imaging studies have shown high contrast between regions rich in mGluR5 levels, such as the anterior cingulated, and regions with low levels, such as the cerebellum and pons, as well as the ability to estimate regional receptor levels using both bolus administration with 2-tissue-compartment modeling and bolus–infusion administration (14,15).
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Transaxial (left) and sagittal (right) BPND images of 18F-FPEB (top) and matching MR images (bottom) in SPM standard space. Regions with high BPND values, namely insular (In), temporal (Tp), and cingulate (Cg) cortices, are indicated on coregistered MR images.

Wong DF1Waterhouse RKuwabara HKim JBrašić JRChamroonrat WStabins MHolt DPDannals RFHamill TGMozley PD18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry. J Nucl Med. 2013 Mar;54(3):388-96.