RESUMO
PURPOSE: Immune checkpoint inhibitor (ICI) monotherapy and combination regimens are being actively pursued as strategies to improve durable response rates in cancer patients. However, the biology surrounding combination therapies is not well understood and may increase the likelihood of immune-mediated adverse events. Accurate stratification of ICI response by non-invasive PET imaging may help ensure safe therapy management across a wide number of cancer phenotypes. PROCEDURES: We have assessed the ability of a fluorine-labelled peptide, [18F]AlF-mNOTA-GZP, targeting granzyme B, to stratify ICI response in two syngeneic models of colon cancer, CT26 and MC38. In vivo tumour uptake of [18F]AlF-mNOTA-GZP following ICI monotherapy, or in combination with PD-1 was characterised and correlated with changes in tumour-associated immune cell populations. RESULTS: [18F]AlF-mNOTA-GZP showed good predictive ability and correlated well with changes in tumour-associated T cells, especially CD8+ T cells; however, overall uptake and response to monotherapy or combination therapies was very different in the CT26 and MC38 tumours, likely due to the immunostimulatory environment imbued by the MSI-high phenotype in MC38 tumours. CONCLUSIONS: [18F]AlF-mNOTA-GZP uptake correlates well with changes in CD8+ T cell populations and is able to stratify tumour response to a range of ICIs administered as monotherapies or in combination. However, tracer uptake can be significantly affected by preexisting phenotypic abnormalities potentially confusing data interpretation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Granzimas/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêutico , Tomografia por Emissão de Pósitrons , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Humanos , Leucócitos/patologia , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Peptídeos/química , Fenótipo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Patients with intra-cerebral metastases often receive glucocorticoids, particularly in the presence of peri-lesional vasogenic cerebral oedema. We present a case of presumptive lung carcinoma with cerebral metastases where central diabetes insipidus was unmasked after glucocorticoid administration and correction of undiagnosed central hypocortisolism.
