Abstract
Current immune monitoring strategies in the clinic are limited in their sensitivity and specificity or struggle to provide precise spatiotemporal information, emphasizing the need for superior imaging probes that can provide macroscopic and accurate assessments of immune cells and their functional states in real time. Lymphocytes, comprising of T cells, B cells, and natural killer (NK) cells, have been a primary focus in the immune imaging field since many of the desired robust, killing responses in cancer immunotherapy and infection converge on these cell types, as does the undesired cytotoxicity observed in autoimmunity and transplant rejection. Identification and targeting of endogenous markers specific to these cells enables their noninvasive visualization in their native environment, bypassing the need for prior isolation or ex vivo radiochemical or genetic manipulation. In this chapter, we highlight nuclear imaging probes that have been developed in the last decade for specific visualization of endogenous biomarkers of lymphocytes, thereby reporting on their distinct behaviors including activation, proliferation, trafficking, inhibition, and cytotoxic effector functions. We discuss how imaging these processes can improve our understanding of local and systemic immune dynamics occurring in cancer immunotherapy and immunopathology and the potential utility of these radioactive probes for improving disease diagnosis, guiding treatment, and evaluating treatment response. Additionally, we discuss the strengths and limitations of these approaches and highlight areas of focus for future studies.
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Acknowledgments
We thank Drs. Federico Simonetta, Carmel T. Chan, Weiyu Chen and Nusrat S. Alam for valuable discussions and for reviewing the manuscript. Additionally we are grateful to Jim Strommer and Judy Schwimmer for their support with figures. We would also like to acknowledge funding support from the Ben and Catherine Ivy Foundation, Canary Foundation and National Cancer Institute (R01 CA201719-05). Finally, we are thankful to our colleagues in the imaging community that contributed to the development and translation of the strategies discussed in this chapter. This work is dedicated to the memory of my father Dr. Mohammed Shamsul Alam, my aunt Dr Dilara Huq and our mentor Professor Sanjiv Sam Gambhir; for their deep commitment to humanity, tireless efforts to serve others and above all for their passion and wonder for science and medicine.
Review Criteria: We have intentionally chosen to highlight studies that have been reported within the last decade with an emphasis on those that have been clinically evaluated or demonstrate strong translational potential. Pubmed was searched for relevant publications up until June 2020. ClinicalTrials.gov was queried for trials pertaining to the probes discussed. We chose to focus on endogenous imaging biomarkers, specifically associated with lymphocytes, rather than general markers associated with the inflammatory response that are upregulated on vasculature and stroma. We recognize that there are many valuable studies in the field that were not within the scope of this discussion and have cited references for readers who are interested in those areas.
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Dr Gambhir was the founder and equity holder of CellSight Inc. that develops and translates strategies for imaging cell trafficking/transplantation.
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Alam, I.S., Shaffer, T.M., Gambhir, S.S. (2022). Nuclear Imaging of Endogenous Markers of Lymphocyte Response. In: Harsini, S., Alavi, A., Rezaei, N. (eds) Nuclear Medicine and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-81261-4_2
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