Imaging tumour hypoxia with positron emission tomography.

Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.Cancer Research UK (CRUK) funded the National Cancer Research Institute (NCRI) PET Research Working party to organise a meeting to discuss imaging cancer with hypoxia tracers and Positron Emission Tomography. IF was funded by CRUK and is also supported by the Chief Scientific Office. ALH is supported by CRUK and the Breast Cancer Research Foundation. RM is funded by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2014610a.html

FDG uptake, a surrogate of tumour hypoxia?

Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-D-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting

Molecular imaging of hypoxia with radiolabelled agents

Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia

<SUP>18</SUP>F-FDG PET/CT features of immune-related adverse events and pitfalls following immunotherapy

18 F-FDG PET/CT scanning is routinely performed to stage and evaluate the treatment response in many malignancies. Immunotherapy is a rapidly growing treatment option for many cancers, and both clinicians and imaging specialists need to be familiar with 18 F-FDG PET/CT imaging characteristics unique to patients on this type of treatment. In particular, many immune-related adverse events (irAEs) can be detected on 18 F-FDG PET/CT and early accurate identification is critical to reduce treatment related morbidity and incorrect interpretation of malignant disease status. This pictorial essay reviews frequently encountered irAEs in clinical practice and their appearances on 18 F-FDG PET/CT along with a brief discussion on pseudoprogression and hyperprogression

Correlation of clinical outcomes with bremsstrahlung and Y-90 PET/CT imaging findings following Y-90 radiosynoviorthesis: a prospective study

BACKGROUND: It is unclear how to predict which patients will respond to Y-90 radiosynoviorthesis. The aim of this study is to correlate clinical outcomes following Y-90 radiosynoviorthesis with bremsstrahlung and Y-90 PET/CT imaging findings. METHODS: Fifty-one joints underwent bremsstrahlung planar and Y-90 PET/CT imaging following Y-90 radiosynoviorthesis. The Y-90 distribution pattern on bremsstrahlung planar imaging was classified as diffuse or non-diffuse and compared with the intra or extra-articular location of activity on Y-90 PET/CT. Treatment response was assessed by patients and clinicians at 6 months. In patients who underwent bremsstrahlung SPECT, side-by-side comparison with PET was performed with image quality/resolution scored using a five-point-scale. FINDINGS: Bremsstrahlung planar images were classified as diffuse in 33/51 (65 %) and non-diffuse in 18/51 (35 %) scans. There was no association between treatment response and the bremsstrahlung planar imaging pattern. PET/CT confirmed an intra-articular location in all 33/33 (100 %) diffuse scans and an extra-articular location in 3/18 (17 %) non-diffuse scans. Of the three joints with extra-articular activity, none had any treatment response. Excluding these three joints, there remained no association between the bremsstrahlung planar imaging pattern and treatment response. Of the 42 joints imaged with SPECT, PET image quality/resolution was classified as superior in 40 (95 %). In one patient with extra-articular activity on PET/CT, SPECT/CT was unable to definitively localise the activity to the intra or extra-articular space. CONCLUSIONS: The distribution pattern on bremsstrahlung planar imaging did not correlate with clinical outcome following Y-90 radiosynoviorthesis in our study population. However, in patients with non-diffuse planar imaging patterns, Y-90 PET/CT should be considered to exclude extra-articular activity with PET providing superior image quality compared to SPECT

Excellent suppression of physiological myocardial FDG activity in patients with cardiac sarcoidosis.

INTRODUCTION: Suppression of physiological myocardial FDG activity is vital in patients undergoing PET/CT for assessment of known or suspected cardiac sarcoidosis. This study aims to evaluate the efficacy of physiological myocardial FDG suppression following a protocol change to a 24-h high fat very low carbohydrate (HFVLC) diet and prolonged fast. METHODS: A retrospective review of patients undergoing FDG PET/CT for the evaluation of cardiac sarcoidosis was performed. Prior to June-2018, patients were prepared with a single very high-fat low carbohydrate meal followed by a 12-18 h fast (group 1). After June-2018, a protocol change was initiated with patients prepared with a HFVLC diet for 24-h followed by a 12-18 h fast (group 2). Focal myocardial activity was classified as positive, absent activity as negative and diffuse/focal on diffuse activity as indeterminate. RESULTS: A total of 94 FDG PET/CT scans were included with 46 scans in group 1 and 48 scans in group 2. Studies were classified as positive, negative or indeterminate in 25 (54%), 7 (15%) and 14 (30%) scans in group 1 and in 13 (27%), 33 (69%) and 2 (4%) scans in group 2, respectively. In scans classified as negative, myocardial FDG activity was less than mediastinal blood pool activity in 5/7 (71%) scans in group 1 and 33/33 (100%) scans in group 2. CONCLUSION: Excellent myocardial FDG suppression can be achieved using a 24-h HFVLC diet and prolonged fast, resulting in a very low indeterminate scan rate in patients with known or suspected cardiac sarcoidosis

Clinical utility of stimulated cholescintigraphy using a standardized Ensure-Plus fatty meal protocol in patients with suspected functional gallbladder disorder: a retrospective study of seven-years clinical experience.

BACKGROUND: The clinical utility of fatty meal stimulated cholescintigraphy particularly using a standardized formulation in patients with suspected functional gallbladder disorder has not been extensively studied. We present our seven-year clinical experience using an Ensure plus protocol. METHODS: A retrospective study was performed on patients undergoing stimulated cholescintigraphy using Ensure Plus for evaluation of suspected functional gallbladder disorder. A gallbladder ejection fraction (GBEF) of <33% was considered abnormal. RESULTS: Of the 173 patients evaluated, 57 (33%) had an abnormal GBEF, 112 (65%) had a normal GBEF and 4 (2%) had no gallbladder visualization. Of the 57 patients with an abnormal GBEF, symptom improvement occurred in 30/31 (97%) who underwent cholecystectomy and in 17/26 (65%) who were managed conservatively (p = 0.003). Of the 112 patients with a normal GBEF, symptom improvement occurred in 8/10 (80%) who underwent cholecystectomy and 74/102 (73%) who were managed conservatively (p = 1.000). In the subgroup of 102 patients with a normal GBEF managed conservatively, those without symptomatic improvement had lower GBEFs compared to those with symptomatic improvement (median GBEF 46% versus 57%, p = 0.019). CONCLUSION: Our retrospective results support a clinical role for stimulated cholescintigraphy using Ensure Plus in the evaluation of patients with suspected functional gallbladder disorder. While an abnormal GBEF predicts good surgical outcome, our results suggest that using an absolute GBEF cut off value of <33% may not apply to all patients and hence GBEF results should only be used as an adjunct in the surgical decision-making process