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

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Abstract
Noninvasively monitoring immune function by positron emission tomography could affect the diagnosis and treatment evaluation of immunological disorders. Progress, however, has been hampered by the lack of probes with distinct biodistribution patterns. Radu et al. exploit the fact that many immune cells utilize a salvage pathway for nucleotide generation during DNA synthesis to develop [18F]FAC (1-(2′-deoxy-2′[18F]fluoroarabinofuranosyl) cytosine), a new probe with increased accumulation in proliferating T cells. Studies in mice show it has advantages over commonly used probes and may be clinically useful. 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.