Positron emission tomography molecular imaging to monitor anti-tumor systemic response for immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICIs) achieve a milestone in cancer treatment. Despite the great success of ICI, ICI therapy still faces a big challenge due to heterogeneity of tumor, and therapeutic response is complicated by possible immune-related adverse events (irAEs). Therefore, it is critical to assess the systemic immune response elicited by ICI therapy to guide subsequent treatment regimens. Positron emission tomography (PET) molecular imaging is an optimal approach in cancer diagnosis, treatment effect evaluation, follow-up, and prognosis prediction. PET imaging can monitor metabolic changes of immunocytes and specifically identify immuno-biomarkers to reflect systemic immune responses. Here, we briefly review the application of PET molecular imaging to date of systemic immune responses following ICI therapy and the associated rationale.

Enhanced Therapeutic Efficacy of Combining Losartan and Chemo-Immunotherapy for Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, which is relatively resistant to anti-programmed cell death-1 (α-PD1) therapy, characterized as non-immunogenic, dense stroma and accumulation of M2 tumor-associated macrophages (TAMs). Despite progress in strategies to deplete extracellular matrix (ECM) and enhance tumor-cell immunogenicity, the combinatorial anti-cancer effects with α-PD1 need to be explored. Here, we applied doxorubicin hydrochloride liposome (Dox-L) as immunogenic cell death (ICD)-inducing nano-chemotherapy and used losartan as stroma-depleting agent to improve α-PD1 efficacy (Losartan + Dox-L + α-PD1). The results showed that losartan could cause ECM reduction, facilitating enhanced delivery of Dox-L and further dendritic cell (DC) maturation. Additionally, losartan could also alleviate hypoxia for TNBC, thus reprogramming pro-cancer M2 TAMs to anti-cancer M1 TAMs, successfully overcoming immune-suppressive microenvironment. These modifications led to a significant increase in T cells' infiltration and augmented anti-tumor immunity as exemplified by the notable reduction in tumor size and lung metastases. In summary, our findings support that combined treatment of losartan with Dox-L normalizes immunological-cold microenvironment, improves immuno-stimulation and optimizes the efficacy of TNBC immunotherapy. A novel combinational strategy with FDA-approved compounds proposed by the study may potentially be useful in TNBC clinical treatment.

Radionuclide imaging of apoptosis for clinical application.

Apoptosis was a natural, non-inflammatory, energy-dependent form of programmed cell death (PCD) that can be discovered in a variety of physiological and pathological processes. Based on its characteristic biochemical changes, a great number of apoptosis probes for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have been developed. Radionuclide imaging with these tracers were potential for the repetitive and selective detection of apoptotic cell death in vivo, without the need for invasive biopsy. In this review, we overviewed molecular mechanism and specific biochemical changes in apoptotic cells and summarized the existing tracers that have been used in clinical trials as well as their potentialities and limitations. Particularly, we highlighted the clinic applications of apoptosis imaging as diagnostic markers, early-response indicators, and prognostic predictors in multiple disease fields.

PET imaging of reactive astrocytes in neurological disorders.

The reactive astrocytes manifest molecular, structural, and functional remodeling in injury, infection, or diseases of the CNS, which play a critical role in the pathological mechanism of neurological diseases. A growing need exists for dependable approach to better characterize the activation of astrocyte in vivo. As an advanced molecular imaging technology, positron emission tomography (PET) has the potential for visualizing biological activities at the cellular levels. In the review, we summarized the PET visualization strategies for reactive astrocytes and discussed the applications of astrocyte PET imaging in neurological diseases. Future studies are needed to pay more attention to the development of specific imaging agents for astrocytes and further improve our exploration of reactive astrocytes in various diseases.