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Cancer immunotherapy (also known as immuno-oncology), a promising anti-cancer strategy by harnessing
the body’s own immune system against cancer, has emerged as the “fifth therapeutic pilla” in the field of
cancer treatment since surgery, chemotherapy, radiation and targeted therapy. Clinical efficacy of several immunotherapies
has been demonstrated in clinical settings, however, only a small subset of patients exhibit dramatic
or durable responses, with the highest reported frequency about 10-40% from single-agent PD-L1/PD-1 inhibitors,
suggesting the urgent need of consistent objective response biomarkers for monitoring therapeutic response
accurately, predicting therapeutic efficacy and selecting responders. Key elements of therapeutic responses to
cancer immunotherapies contain the cancer cell response and the alternation of inherent immunological characteristics.
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Here, we document the literature regarding imaging the key elements of therapeutic responses to cancer immunotherapies
using PET. We discussed PET imaging approaches according to different response mechanisms underlying
diverse immune-therapeutic categories, and also highlight the ongoing efforts to identify novel immunotherapeutic
PET imaging biomarkers. In this article, we show that PET imaging of the key elements of therapeutic
responses to cancer immunotherapies using PET can allow for more precise prediction, earlier therapy response
monitoring, and improved management. However, all of these strategies need more preclinical study and clinical
validation before further development as imaging indicators of the immune response.
SCO‐267 is a GPR40 full agonist that has been developed for the treatment of diabetes. To support its preclinical and clinical development, in this study, we developed an ultra‐high performance liquid chromatography tandem mass spectrometric method for the determination of SCO‐267 in dog plasma using cabozantinib as internal standard (IS). The chromatographic separation was obtained on a Waters acquity BEH C18 column (50 × 2.1 mm, i.d., 1.7 μm) and the detection was performed using Thermo TSQ triple quadrupole mass spectrometer with multiple reaction monitoring positive mode at m/z 615.3 > 230.1 for SCO‐267 and m/z 502.5 > 323.3 for IS. The method was validated over the concentration range of 1–2,000 ng/ml with the lower limit of quantification of 1 ng/ml. The selectivity, linearity, precision and accuracy over this range were acceptable. The extraction recovery was more than 88.73% and no matrix effect was observed. SCO‐267 was demonstrated to be stable during the storage and processing period. The new method was successfully applied to the pharmacokinetic study in beagle dogs following a single oral and intravenous administration. The oral bioavailability was 64.34%. In addition, the metabolites from dog liver microsomal incubation and plasma collected after an oral administration were identified by a UHPLC–HRMS method. The biotransformation pathways of SCO‐267 involved oxygenation, O‐demethylation, N‐dealkylation and acyl glucuronidation.
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