Chimeric antigen receptor T cell therapy (CAR-T) has been rolled out as a new treatment for hematological malignancies. For solid tumor treatment, CAR-T has been disappointing so far. Challenges include the quantification of CAR-T trafficking, expansion and retention in tumors, activity at target sites, toxicities, and long-term CAR-T survival. Non-invasive serial in vivo imaging of CAR-T using reporter genes can address several of these challenges. For clinical use, a non-immunogenic reporter that is detectable with exquisite sensitivity by positron emission tomography (PET) using a clinically available non-toxic radiotracer would be beneficial. Here, we employed the human sodium iodide symporter to non-invasively quantify tumor retention of pan-ErbB family targeted CAR-T by PET. We generated and characterized traceable CAR T cells and examined potential negative effects of radionuclide reporter use. We applied our platform to two different triplenegative breast cancer (TNBC) models and unexpectedly observed pronounced differences in CAR-T tumor retention by PET/CT (computed tomography) and confirmed data ex vivo. CAR-T tumor retention inversely correlated with immune checkpoint expression in the TNBC models. Our platform enables highly sensitive non-invasive PET tracking of CAR-T thereby addressing a fundamental unmet need in CAR-T development and offering to provide missing information needed for future clinical CAR-T imaging.

Microscopy and medical imaging are related in their exploitation of electromagnetic waves, but were developed to satisfy differing needs, namely to observe small objects or to look inside subjects/objects, respectively. Together, these techniques can help elucidate complex biological processes and better understand health and disease. A current major challenge is to delineate mechanisms governing cell migration and tissue invasion in organismal development, the immune system and in human diseases such as cancer where the spatiotemporal tracking of small cell numbers in live animal models is extremely challenging. Multi-modal multi-scale in vivo cell tracking integrates medical and optical imaging. Fuelled by basic research in cancer biology and cell-based therapeutics, it has been enabled by technological advances providing enhanced resolution, sensitivity and multiplexing capabilities. Here, we review which imaging modalities have been successfully used for in vivo cell tracking and how this challenging task has benefitted from combining macroscopic with microscopic techniques.

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Psychosocial stress is a risk factor for the development of depression. Recent evidence suggests that glial activation could contribute to the development of depressive-like behaviour. This study aimed to evaluate in vivo whether repeated social defeat (RSD) induces short-and long-term inflammatory and metabolic alterations in the brain through positron emission tomography (PET). Male Wistar rats (n ¼ 40) were exposed to RSD by dominant Long-Evans rats on five consecutive days. Behavioural and biochemical alterations were assessed at baseline, day 5/6 and day 24/25 after the RSD protocol. Glial activation ( 11 C-PK11195 PET) and changes in brain metabolism ( 18 F-FDG PET) were evaluated on day 6, 11 and 25 (short-term), and at 3 and 6 months (long-term). Defeated rats showed transient depressive-and anxietylike behaviour, increased corticosterone and brain IL-1b levels, as well as glial activation and brain hypometabolism in the first month after RSD. During the third-and six-month follow-up, no between-group differences in any investigated parameter were found. Therefore, non-invasive PET imaging demonstrated that RSD induces transient glial activation and reduces brain glucose metabolism in rats. These imaging findings were associated with stress-induced behavioural changes and support the hypothesis that neuroinflammation could be a contributing factor in the development of depression.