METABOLISM

 

All living cells need energy and building blocks such as sugars, lipids, nucleic acids, and amino acids. With disease and with response to treatment, metabolism often precedes anatomic alterations. Changes in metabolism are seen in cancer, cardiovascular disease, autoimmunity, and neurodegeneration. Moreover, modulating cellular metabolism is of growing interest as a vital and complementary approach in cancer treatment. We have imaged all of the listed diverse cellular building blocks in both murine models and in humans to improve disease detection, monitor response to therapy, and to help define optimal therapeutic targets in various scenarios.

 


 

In the Division of Precision Medicine we study how metabolic imaging agents ranging from sugars to nucliec acids can be used to predict and monitor disease.

Recently, we have utilized two clinically-established metabolic imaging agents, 18F-FDG and 18F-FLT to demonstrate that metabolism altering drugs like metformin alter tumor metabolism. Our work, published in the Journal of Nuclear Medicine, has helped to prove increased glucose metabolism (A) and decreased overall proliferation (B) is detectable and quantifiable by PET imaging. These results suggest 18FDG uptake may be misleading, and that 18FLT may be a more appropriate tool for analyzing metformin effectiveness.

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Habibollahi P, van den Berg NS, Kuruppu D, Loda M, Mahmood U. Metformin--an Adjunct Antineoplastic Therapy--Divergently Modulates Tumor Metabolism and Proliferation, Interfering with Early Response Prediction by 18F-FDG PET Imaging. J Nucl Med. 2013 Feb; 54(2):252-8.PubMed


In another collaborative effort, our group utilized the radiolabeled metabolite 11C-Acetate to monitor the effective of several small molecule inhibitors of AMPK, a critical protein in metabolic regulation, on fatty acid synthesis . Our data, as shown in EMBO Molecular Medicine, illutstrate that the tested inhibitors do not effect over all 11C uptake, only fatty acid synthesis, which is consitsent with the in vitro biological data.


C11 Acetate Image 

Zadra G, Photopoulos C, Tyekucheva S, Heidari P, Weng QP, Fedele G, Liu H, Scaglia N, Priolo C, Sicinska E, Mahmood U, Signoretti S, Birnberg N, Loda M. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014 Apr;6(4):519-38. Pubmed


We believe that molecular imaging of metabolism will be a vital part of characterizing an individual's malignancy, and thus are excited to continue contributing to this individual aspect of Precision Medicine.