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Background: Brain metastases (BM) are the most frequent malignant brain tumors. The aim of this study was to characterize the tumor microenvironment (TME) of BM and particularly hypoxia and redox state, known to play a role in tumor growth and treatment resistance with multimodal PET and MRI imaging, immunohistochemical and proteomic approaches in a human lung cancer (H2030-BrM3)-derived BM model in rats. Results: First, in vitro studies confirmed that H2030-BrM3 cells respond to hypoxia with increasing expression of HIF-1, HIF-2 and their target genes. Proteomic analyses revealed, among expression changes, proteins associated with metabolism, oxidative stress, metal response and hypoxia signaling in particular in cortical BM. [64Cu][Cu(ATSM)] PET revealed a significant uptake by cortical BM (p < 0.01), while no uptake is observed in striatal BM 23 days after tumor implantation. Pimonidazole, HIF-1α, HIF-2α, CA-IX as well as GFAP, CTR1 and DMT1 immunostainings are positive in both BM. Conclusion: Overall, [64Cu][Cu(ATSM)] imaging and proteomic results showed the presence of hypoxia and protein expression changes linked to hypoxia and oxidative stress in BM, which are more pronounced in cortical BM compared to striatal BM. Moreover, it emphasized the interest of [64Cu][Cu(ATSM)] PET to characterize TME of BM and depict inter-metastasis heterogeneity that could be useful to guide treatments. [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether artificial intelligence (AI)-based denoising halves PET acquisition time in digital PET/CT. Methods: One hundred ninety-five patients referred for [18F]FDG PET/CT were prospectively included. Body PET acquisitions were performed in list mode. Original "PET90" (90 s/bed position) was compared to reconstructed ½-duration PET (45 s/bed position) with and without AI-denoising, "PET45AI and PET45". Denoising was performed by SubtlePET™ using deep convolutional neural networks. Visual global image quality (IQ) 3-point scores and lesion detectability were evaluated. Lesion maximal and peak standardized uptake values using lean body mass (SULmax and SULpeak), metabolic volumes (MV), and liver SULmean were measured, including both standard and EARL1 (European Association of Nuclear Medicine Research Ltd) compliant SUL. Lesion-to-liver SUL ratios (LLR) and liver coefficients of variation (CVliv) were calculated. Results: PET45 showed mediocre IQ (scored poor in 8% and moderate in 68%) and lesion concordance rate with PET90 (88.7%). In PET45AI, IQ scores were similar to PET90 (P = 0.80), good in 92% and moderate in 8% for both. The lesion concordance rate between PET90 and PET45AI was 836/856 (97.7%), with 7 lesions (0.8%) only detected in PET90 and 13 (1.5%) exclusively in PET45AI. Lesion EARL1 SULpeak was not significantly different between both PET (P = 0.09). Lesion standard SULpeak, standard and EARL1 SULmax, LLR and CVliv were lower in PET45AI than in PET90 (P < 0.0001), while lesion MV and liver SULmean were higher (P < 0.0001). Good to excellent intraclass correlation coefficients (ICC) between PET90 and PET45AI were observed for lesion SUL and MV (ICC ≥ 0.97) and for liver SULmean (ICC ≥ 0.87). Conclusion: AI allows [18F]FDG PET duration in digital PET/CT to be halved, while restoring degraded ½-duration PET image quality. Future multicentric studies, including other PET radiopharmaceuticals, are warranted. [ABSTRACT FROM AUTHOR]

Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme. Methods: MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([F]FDG and [F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival. Results: Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [F]FLT uptake, cerebral blood volume and oedema. [F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy. Conclusion: The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations. [ABSTRACT FROM AUTHOR]