Intratumoral genetic heterogeneity and the role of metabolic reprogramming in renal cell carcinoma have been extensively documented. However, the distribution of these metabolic changes within the tissue has not been explored. We report on the first-in-human in vivo non-invasive metabolic interrogation of renal cell carcinoma using hyperpolarized carbon-13 (13C) MRI and describe the validation of in vivo lactate metabolic heterogeneity against multi regional ex vivo mass spectrometry. hyperpolarized carbon-13 (13C)-MRI provides an in vivo assessment of metabolism and provides a novel opportunity to safely and non-invasively assess cancer heterogeneity.

Background: The aim of this study was to translate dynamic glucose enhancement (DGE) body magnetic resonance imaging (MRI) based on the glucose chemical exchange saturation transfer (glucoCEST) signal to a 3 T clinical field strength. Methods: An infusion protocol for intravenous (i.v.) glucose was optimised using a hyperglycaemic clamp to maximise the chances of detecting exchange-sensitive MRI signal. Numerical simulations were performed to define the optimum parameters for glucoCEST measurements with consideration to physiological conditions. DGE images were acquired for patients with lymphomas and prostate cancer injected i.v. with 20% glucose. Results: The optimised hyperglycaemic clamp infusion based on the DeFronzo method demonstrated higher efficiency and stability of glucose delivery as compared to manual determination of glucose infusion rates. DGE signal sensitivity was found to be dependent on T 2 , B 1 saturation power and integration range. Our results show that motion correction and B 0 field inhomogeneity correction are crucial to avoid mistaking signal changes for a glucose response while field drift is a substantial contributor. However, after B 0 field drift correction, no significant glucoCEST signal enhancement was observed in tumour regions of all patients in vivo. Conclusions: Based on our simulated and experimental results, we conclude that glucose-related signal remains elusive at 3 T in body regions, where physiological movements and strong effects of B 1 + and B 0 render the originally small glucoCEST signal difficult to detect.

Gastric cancer (GC) represents a major cancer burden worldwide, and remains the second leading cause of cancer-related death. Due to its insidious nature, presentation is usually late and often carries a poor prognosis. Despite having improved treatment modalities over the last decade, for most patients only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and its signaling pathways, offers the hope of clinically significant promising advances for selected groups of patients. Patients with Her-2 overexpression or amplification have experienced benefit from the integration of monoclonal antibodies such as trastuzumab to the standard chemotherapy. Additionally, drugs targeting angiogenesis (bevacizumab, sorafenib, sunitinib) are under investigation and other targeted agents such as mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors are in preclinical or early clinical development. Patient selection and the development of reliable biomarkers to accurately select patients most likely to benefit from these tailored therapies is now key. Future trials should focus on these advances to optimize the treatment for GC patients. This article will review recent progress and current status of targeted agents in GC.

Cardiovascular disease continues to be a major burden facing healthcare systems worldwide. In the developed world, cardiovascular magnetic resonance (CMR) is a well-established non-invasive imaging modality in the diagnosis of cardiovascular disease. However, there is significant global inequality in availability and access to CMR due to its high cost, technical demands as well as existing disparities in healthcare and technical infrastructures across high-income and low-income countries. Recent renewed interest in low-field CMR has been spurred by the clinical need to provide sustainable imaging technology capable of yielding diagnosticquality images whilst also being tailored to the local populations and healthcare ecosystems. This review aims to evaluate the technical, practical and cost considerations of low field CMR whilst also exploring the key barriers to implementing sustainable MRI in both the developing and developed world.

We present the case of a patient with Lynch syndrome and metastatic colorectal carcinoma (mCRC). The initial immunohistochemistry (IHC) test for deficient mismatch repair gave a false negative result. However, the same mutation has accurately has been detected with IHC in other cancers with microsatellite instability (MSI) This supports the determining role of somatic missense mutations in MMR IHC. MSI-PCR testing confirmed MSI and the patient benefited from nivolumab with a complete metabolic response. We explain the rationale for immunotherapy in mCRC, current testing strategies and discuss future developments in MSI testing. We advocate for upfront testing using both IHC and MSI-PCR to direct therapy in mCRC, and a greater understanding of IHC and MSI-PCR testing pitfalls.

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BackgroundAccurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer.Methods/designThe LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort.DiscussionThe LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway.Trial registrationLOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.

Radiolabelled prostate-specific membrane antigen (PSMA)-based Positron emission tomography-computed tomography (PET-CT) has been shown in numerous studies to be superior to conventional imaging in the detection of nodal or distant metastatic lesions. 68Ga-PSMA PET-CT is now recommended by many guidelines for the detection of biochemically relapsed disease after radical local therapy. PSMA radioligands can also function as radiotheranostics, namely Lu-PSMA has been shown to be a potential new line of treatment for metastatic castrate resistant prostate cancer. W hole-body MRI (WB-MRI) has been shown to have a high diagnostic performance in the detection and monitoring of metastatic bone disease. Prospective, randomized, multi-centre studies comparing 68 Ga-PSMA PET-CT and WB-MRI for pelvic nodal and metastatic disease detection are yet to be performed. Challenges for interpretation of PSMA include tracer trapping in non-target tissues and urinary excretion of tracers confounding image interpretation at the vesicoureteral junction. Additionally , studies have described how long-term androgen deprivation therapy (ADT) affects PSMA expression and could, therefore, reduce tracer uptake and visibility of PSMA-positive lesions . Furthermore, ADT of short duration might increase PSMA expression, leading to the PSMA flare phenomenon, which makes it challenging to accurately monitor treatment response to ADT with PSMA-PET. Scan duration, detection of incidentalomas and presence of metallic implants are some of the major challenges with WB-MRI. Emerging data supports the wider adoption of PSMA-PET and WB-MRI for diagnosis, staging, disease burden evaluation and response monitoring, though their relative roles in the standard of care management of patents is yet to be fully defined.. Key points• Next-generation imaging techniques have been found to affect prostate cancer disease state classifications as their increased sensitivity can result in stage migration.