Learning Points and Speculation on Future Directions for Imaging Immune System with 18F-FDG and New Tracers
| Point | Description |
| 1 | Type of ICI may impact rate of pseudoprogression, with lower rate reported in anti-PD-1/PD-L1 than in anti-CTLA-4 |
| 2 | Rate of pseudoprogression may differ depending on tumor type, with highest rate reported in melanoma, which also has one of highest response rates |
| 3 | Early after commencement of ICIs, change in metabolic parameters on 18F-FDG PET/CT may further predict response in patients with stable morphologic imaging |
| 4 | Although pseudoprogression most commonly occurs within 12 wk of starting ICIs, about of one third happen beyond 12 wk; therefore, timing of first follow-up scan may be important |
| 5 | Early and marked metabolic response with or without morphologic response commonly indicates durable response |
| 6 | 18F-FDG PET/CT performed for response monitoring should also be thoroughly interrogated for manifestations of immune-related adverse events |
| 7 | It appears that number and size of new lesions on 18F-FDG PET/CT are important factors in differentiating true progression from pseudoprogression |
| 8 | Whole-body metabolic tumor volume on 18F-FDG PET/CT is promising metabolic parameter at baseline or during treatment. At baseline, high whole-body metabolic tumor volume is associated with hyperprogressive disease and may be predictive of adverse overall survival |
| 9 | 18F-FDG PET/CT may have role in further risk stratification of patients who achieve partial response on morphologic imaging, hence guiding length of immunotherapy |
| 10 | 18F-FDG PET/CT may have role in patients with dissociated or mixed response on morphologic imaging, to guide local treatment to limited sites of progressive disease while continuing immunotherapy |
| 11a | Decision to continue immunotherapy beyond progression on either morphologic or 18F-FDG PET/CT criteria should be made with caution and considered in selected patients who do not experience severe toxicity from these agents and whose disease-related symptoms have improved or stabilized on treatment |
| 11b | If immunotherapy is continued or there is any doubt about imaging findings, to differentiate pseudoprogression from true progression biopsy or confirmatory scan at short interval (4 wk) may be helpful or, immune-PET targeting activated CD8+ T cells, such as 18F-Ara-G or 68Ga-granzyme B can be considered; 3′-18F-fluoro-3′-deoxythymidine PET/CT may have a role in differentiating pseudoprogression from hyperprogression. |
| 13 | Immune-PET targeting CD8+ T cells may distinguish immune-desert from immune-inflamed tumors, whereby allowing rational selection of ICIs or combination ICIs |
| 14 | 18F-Ara-G and 68Ga-granzyme are promising tracers that can differentiate activated CD8+ T cells from exhausted CD8+ T cells |
| 15 | After pharmacologic intervention or radiotherapy, serial immune-PET targeting CD8+ T cells, including 18F-Ara-G or 68Ga-granzyme, may allow monitoring of T-cell trafficking within tumor sites |
| 16 | Radiolabeled tracers targeting PD1/PD-L1 can demonstrate inter- and intrapatient heterogeneity of these immune checkpoints and can potentially be predictive of response to ICIs but are subject to inherent limitation of PD1/PD-L1 as predictive biomarkers |