TABLE 4.
Novel PET probes for immunotherapy.
| Probe | Target | Study | PET probe | Experiment stage (subject) | Characteristics |
|---|---|---|---|---|---|
| Anti-PD-1 antibody | PD-1-expressing tumor-infiltrating lymphocyte | Liu et al., 2021 (Liu et al., 2021) | 68Ga-NOTA-Nb109 | Preclinical experiment (cell and animal models bearing different tumors) | 68Ga-NOTA-Nb109 can specifically target endogenous PD-L1 and dynamic monitoring of the change of PD-L1 expression and could guide the immunotherapy and immunochemotherapy for refractory cancers |
| Kelly et al., 2021 (Kelly et al., 2021) | 89Zr-REGN3504 | Preclinical experiment (mice and monkeys) | 1.89Zr-REGN3504 specifically localized to spleen and lymph nodes in the PD-1/PD-L1 humanized mice | ||
| 2.89Zr-REGN3504 immuno-PET accurately detected a significant reduction in splenic PD-L1 positive cells following systemic treatment | |||||
| Niemeije et al., 2021 (Niemeijer et al., 2021) | 89Z-pembrolizumab | Clinical experiment (NSCLC patients) | A significant correlation between the grade of uptake of the traces and the response assessed after 3 months of nivolumab was observed | ||
| Li et al., 2020 (Li et al., 2021) | 89Zr-N-sucDf-pembrolizumab | Preclinical experiment (healthy cynomolgus monkeys) | Preferential uptake in the lymphoid tissues, including the lymph nodes, spleen, and tonsils, was shown | ||
| England et al., 2018 (England et al., 2018) | 89Zr-DF nivolumab | Preclinical experiment | There was highly specific binding of 89Zr-DF nivolumab to activated T-cell infiltrating tumors in humanized murine models | ||
| Cole et al., 2017 (Cole et al., 2017) | 89Zr-nivolumab (BMS-936558) | Preclinical experiment (healthy non-human primates) | A study of biodistribution and clearance of BMS-936558 in animals | ||
| Anti-PD-L1 antibody | PD-L1-expressing tumor cell | Laffon et al., 2021 (Laffon and Marthan, 2021) | 18F-BMS-986192 | Clinical experiment (NSCLC patients) | A quantitative research: the ratio of SUV normalized for body weight to plasma concentration might be probed as a complementary possible simplified parameter, that is correlated with Ki/(kb + λ) within 50–55 min after injection |
| Huisman et al., 2020 (Huisman et al., 2020) | 18F-BMS-986192 (anti-PD-L1 adnectin) | Clinical experiment (NSCLC patients), quantitative research | SUV normalized for body weight at 60 min after injection may be a relevant simplified parameter to quantify tumor uptake for baseline PET studies | ||
| Bridgwater et al., 2018 (Bridgwater et al., 2020) | 89Zr-Df-F (ab')2 | Preclinical experiment (Melanoma Mouse Mode) | PET/CT images clearly showed that 89Zr-Df-F (ab')2 possessed superior pharmacokinetics and imaging contrast over the radiolabeled full antibody, with much earlier and higher tumor uptake (5.5 times more at 2 h after injection) and much lower liver background (51% reduction at 2 h after injection) | ||
| Truillet et al., 2018 (Truillet et al., 2018) | 89Zr-C4 | Preclinical experiment | 1.89Zr-C4 can specifically detect antigen in human NSCLC and prostate cancer models endogenously expressing a broad range of PD-L1 | ||
| 2.89Zr-C4 detects mouse PD-L1 expression changes in immunocompetent mice, suggesting that endogenous PD-1/2 will not confound human imaging | |||||
| 3.89Zr-C4 could detect acute changes in tumor expression of PD-L1 due to standard of care chemotherapies | |||||
| Bensch et al., 2018 (Bensch et al., 2018) | 89Zr-atezolizumab | Clinical experiment (bladder cancer, NSCLC, or TNBC patients) | 1. Tumor uptake was generally high but heterogeneous, varying within and among lesions, patients, and tumor types. 2. Clinical responses in patients were better correlated with pretreatment PET signal than IHC- or ribonucleic acid-sequencing-based biomarkers | ||
| Xing et al., 2019 (Xing et al., 2019) | 99mTc-NM-01 | Clinical experiment (NSCLC patients) | 1. Intra-tumoral and inter-tumoral heterogeneity was observed | ||
| 2. Primary tumor: blood-pool ratios at 2 h correlated with IHC. | |||||
| Anti-CTLA-4 antibodies | CTLA-4-expressing activated T cells and some tumor cells | Ehlerding et al., 2019 (Ehlerding et al., 2019) | 64Cu-NOTA-ipilimumab-F (ab')2 | Preclinical experiment (mice) | PET imaging with both 64Cu-NOTA-ipilimumab and 64Cu-NOTA-ipilimumab-F (ab')2 was able to localize CTLA-4+ tissues |
| Ehlerding et al., 2017 (Ehlerding et al., 2017) | 64Cu-DOTA- ipilimumab | Preclinical experiment (mouse models of NSCLC) | 64Cu-DOTA- ipilimumab can correctly localize the tumor, but a link was found with the receptor on the cell surface rather than in the intracellular domain | ||
| Anti-interferon-γ | Activated lymphocytes inside tumor lesions | Gibson et al., 2018 (Gibson et al., 2018) | 89Zr-anti-IFN-γ | Preclinical experiment (mouse with mammary tumors) | The activation status of cytotoxic T cells is annotated by 89Zr-anti-IFN-γ PET, providing valuable non-invasive insight into the function of immune cells in situ |
| Protease granzyme B | Cytotoxic CD8+ T cells and natural killer cells | Larimer et al., 2017 (Larimer et al., 2017) | 68Ga-NOTA-GZP | Preclinical experiment (human melanoma specimens) | Granzyme B PET imaging can serve as a quantitatively useful predictive biomarker for efficacious responses to cancer immunotherapy |
| Interleukin-2 | Tumor/tissue infiltrating T lymphocytes | Markovic et al., 2018 (Markovic et al., 2018) | 99mTc-HYNIC-IL-2 | Clinical experiment (melanoma patients with ipilimumab or pembrolizumab) | 1. Safety and feasibility are verified |
| 2. Detect TIL and distinguish between true progression from HPD. |
PET: positron emission tomography; PD-1: programmed cell death 1; PD-L1: programmed cell death ligand 1; NSCLC: non–small cell lung cancer; SUV: standardized uptake value; CT: computed tomography; PET/CT: positron emission tomography/computed tomography; TNBC: triple-negative breast cancer; IHC: immunohistochemistry; CTLA-4: cytotoxic T-lymphocyte associated-protein 4; IFN: interferon; IL-2: interleukin-2; TIL: tumor lymphocyte infiltration; HPD: hyper-progression.