Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2′-deoxycytidine analog

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Monitoring immune function with molecular imaging could have a considerable impact on the diagnosis and treatment evaluation of immunological disorders and therapeutic immune responses. Positron emission tomography (PET) is a molecular imaging modality with applications in cancer and other diseases. PET studies of immune function have been limited by a lack of specialized probes. We identified [18F]FAC (1-(2′-deoxy-2′-[18F]fluoroarabinofuranosyl) cytosine) by differential screening as a new PET probe for the deoxyribonucleotide salvage pathway. [18F]FAC enabled visualization of lymphoid organs and was sensitive to localized immune activation in a mouse model of antitumor immunity. [18F]FAC microPET also detected early changes in lymphoid mass in systemic autoimmunity and allowed evaluation of immunosuppressive therapy. These data support the use of [18F]FAC PET for immune monitoring and suggest a wide range of clinical applications in immune disorders and in certain types of cancer.

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Figure 1: Identification of fluorinated deoxycytidine analogs retained in activated versus naive T cells.
Figure 2: [18F]FAC has better selectivity for lymphoid organs compared with other PET probes for nucleoside metabolism and glycolysis.
Figure 3: Increased [18F]FAC retention in spleen and lymph nodes at the peak of the primary antitumor immune response.
Figure 4: [18F]FAC microPET-CT allows visualization of increased lymphoid mass in systemic autoimmunity and can be used to monitor immunosuppressive therapeutic interventions.


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We are grateful to D. Stout, W. Ladno and J. Edwards for microPET imaging and to the chemists and cyclotron group for production of PET probes. We thank G. Toy, M. Riedinger, S. Quan, D. Chen, J. Wengrod, D. Goldstein and A. Tran for outstanding technical assistance. We thank J. Lee for the analysis of the microarray data, H. Su for imaging of the U87 tumors, J. Liu and C. Shen for help with biochemical analyses, J. McLaughlin (UCLA) for providing leukemic animal models for imaging studies, and J. Czernin, H. Herschman and A. Ribas for insightful discussions. We also thank B. Anderson for help with preparing the manuscript. O.N.W. is an investigator of the Howard Hughes Medical Institute. C.G.R. was supported by In Vivo Cellular and Molecular Imaging Centers Developmental Project Award, grant NIH P50 CA86306 from the National Cancer Institute at the US National Institutes of Health, by US National Cancer Institute grant 5U54 CA119347 and by Juvenile Diabetes Research Foundation Award 17-2006-870. C.G.R. acknowledges unrestricted support from Merck Research Laboratories. C.J.S. was supported by a Fred Eiserling and Judith Lengyel Graduate Doctorate Fellowship. E.N.-G. was supported by the US National Institutes of Health T32 GM08042 UCLA Medical Scientist Training Program. This research was supported in part by US Department of Energy Contract DE-FG02-06ER64249 (M.E.P.), by US National Cancer Institute grant R24CA92865 and by funds from the Samuel Waxman Cancer Research Foundation and the W.M. Keck Foundation.

Author information

C.G.R., C.J.S., E.N.-G., N.S., J.R.B., M.E.P. and O.N.W. designed research; C.G.R., C.J.S., E.N.-G., N.S. and S.M.S. performed research; C.G.R., C.J.S., E.N.-G., N.S., S.M.S. and O.N.W. analyzed data; C.G.R., C.J.S. and O.N.W. wrote the paper.

Correspondence to Caius G Radu or Owen N Witte.

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Portions of the work covered in this manuscript have been disclosed to the University of California, Los Angeles Office of Intellectual Property Administration and included in patent applications to the US Patent Office.

Supplementary information

Supplementary Text and Figures

Supplementary Figs. 1–8 and Supplementary Methods (PDF 2372 kb)

Supplementary Movie 1

[18F]FAC biodistribution during the first 3 min after injection. (MOV 1899 kb)

Supplementary Movie 2

[18F]FAC biodistribution 3–10 min after injection. (MOV 2195 kb)

Supplementary Movie 3

[18F]FAC biodistribution 10–30 min after injection. (MOV 2290 kb)

Supplementary Movie 4

[18F]FAC biodistribution 30–60 min after injection. (MOV 2008 kb)

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