Protocol for a MULTI-centre feasibility study to assess the use of 99mTc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study).

INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.

Identification of specific SUVmax ratios enhances diagnostic accuracy for staging of intrathoracic nodes in lung cancer.

INTRODUCTION: Studies demonstrating limited accuracy of 'positive' and 'negative' lymph nodes on fluorodeoxyglucose (FDG) PET-CT in staging for lung cancer have led to guidelines stating mediastinal nodes enlarged on computed tomography, irrespective of FDG uptake, require endobronchial ultrasound (EBUS)-transbronchial needle aspiration (TBNA). However FDG uptake occurs on a continuous spectrum and the use of standardised uptake value (SUV)max ratios, rather than a binary classification, may have improved diagnostic accuracy. METHODS: This was a retrospective analysis of patients with lung cancer who had PET-CT and EBUS-TBNA in 2015-2018. Results from EBUS and the SUVmax ratio of sampled lymph nodes to mediastinal blood pool (SUVmax LN/MBP) were analysed. RESULTS: From 99 patients 102 malignant and 54 benign nodes were identified. The SUVmax range was 2.5-52 for malignant and 1.6-5.4 for benign nodes. The SUVmax LN/MBP was 1.3-23 for malignant and 0.7-2.3 for benign nodes. All nodes with SUVmax LN/MBP <1.3 were benign with 100% negative predictive value (NPV). All nodes with SUVmax LN/MBP >2.3 were malignant with 100% positive predictive value (PPV). CONCLUSION: In this relatively small sample, SUVmax LN/MBP <1.3 had a NPV of 100% for excluding malignant nodes and SUVmax LN/MBP >2.3 had a PPV of 100% for diagnosing malignant nodes. Using SUVmax ratios could obviate the need for staging EBUS in selected patients with resultant time and cost savings. Selecting different SUVmax ratios, chosen to provide high accuracies for the parameter of interest to change management, is a potentially powerful diagnostic tool that is overlooked when FDG uptake is only classified as 'positive' or 'negative'.

Theranostics in neuroendocrine tumours: somatostatin receptor imaging and therapy.

Theranostics and its principles: pre-treatment selection of patients who are most likely to benefit from treatment by the use of a related, specific diagnostic test are integral to the treatment of patients with neuroendocrine tumours (NETs). This is due to NETs' important, but variable, somatostatin receptor (SSTR) expression, their heterogeneity and variation in site of primary and rate of progression. Only patients whose tumours have sufficient expression of SSTRs will benefit from SSTR-based radionuclide therapy and demonstrating this expression prior to therapy is essential. This article provides a relevant overview of NETs and the multiple facets of SSTR based theranostics, including imaging and therapy radionuclides; clinical efficacy and toxicity; patient selection and treatment and finally emerging radiopharmaceuticals and newer clinical applications.

Determining the Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission/Computed Tomography in Detecting Prosthetic Aortic Graft Infection.

BACKGROUND: To determine the diagnostic value of 18F-fluorodeoxyglucose positron emission/computed tomography (FDG PET/CT) in detecting prosthetic aortic graft infection (AGI). METHODS: Twenty-one patients with prosthetic grafts for abdominal aortic aneurysms underwent FDG PET/CT scans for suspected graft infection over a 15-month period. Images were evaluated for tracer pattern and grade of FDG uptake in addition to measuring the maximal standardized uptake value (SUVmax). Two independent nuclear medicine physicians retrospectively evaluated all imaging. The images from a control group of patients with aortic grafts who underwent FDG PET/CT scans for onco-hematological indications were evaluated to establish radiological characteristics of asymptomatic grafts. Secondary parameters that are associated with graft infection such as components of the peripheral blood count were collected. Graft infection status was determined using microbiological outcomes following graft explantation or radiological drainage of perigraft collections and correlated with results of the FDG PET/CT scans to determine infective status. RESULTS: In the control group, the pattern of FDG uptake was homogenous and diffuse. The mean SUVmax was 3.5 (±1.3). Thirteen out of 21 grafts were confirmed as infected. Tracer uptake in infected grafts displayed an intense and focal pattern, with a median grade of uptake of 4 vs. 2 on a validated 4 point grading scale. The area under the receiver operating curve for FDG PET/CT in detecting infection was 0.85 (±0.15) P = 0.01. Sensitivity was 92%, specificity 63%, and positive and negative predictive values of 80% and 83%, respectively. The SUVmax was significantly higher in infected than noninfected grafts, (10.3 ± 4.2 vs. 5.4 ± 3.4) P = 0.02. According to the receiver operating characteristic analysis, SUVmax greater than 6.3 represented the optimal cutoff between infective and noninfective outcome. Of the secondary parameters collected, grade of uptake and SUVmax were the only significant predictors of infection (odds ratio 2.5, 1.5 respectively) P = 0.05. White cell count, erythrocyte sedimentation rate, and C-reactive protein demonstrated nonsignificant odds ratios of 1.4, 0.9, and 1.0, respectively. CONCLUSIONS: FDG PET/CT is a valuable diagnostic test for identifying AGI. Infected grafts display significantly greater FDG uptake in a distinctive intense focal perigraft pattern and distribution. SUVmax greater than 6.3 is a good cutoff to determine infective status.

Evidence-based management of incidental focal uptake of fluorodeoxyglucose on PET-CT.

Focal incidental uptake, with or without CT abnormalities, is a common finding on fluorodeoxyglucose PET/CT and evidence-based management for this type of uptake is lacking. This article reviews the evidence on focal incidental uptake including the incidence of malignancy, differential diagnosis and imaging criteria which can be used to further characterize it. The article focusses on PET rather than CT criteria. The strength of the evidence base is highly variable ranging from systematic reviews and meta-analyses to a virtual absence of evidence. Caution needs to be used when using standardized uptake values (SUVs) reported in other studies due to interpatient and institution observed variation in SUVs. There is sufficient evidence to permit specific suggestions on how to interpret the foci and recommend further management in the: pituitary (investigate when SUVmax >4.1), thyroid (investigate all), breast (investigate all), lung parenchyma (if focus of fluorodeoxyglucose without a CT nodule, no further investigations), colon (investigate all foci with SUVmax >5.9, urgently if SUVmax >11.4), adrenals (criteria depend on if patient has cancer) and prostate gland (investigate in males aged >50 years or >40 years if peripheral uptake or patient has other risk factors). There is some evidence to guide further management for the parotid gland, naso-orophaynx, oesophagus, pancreas, uterus and ovaries. There is insufficient evidence to guide management for the liver, spleen, kidneys, gallbladder, testis and bone, for these organs patient characteristics and other guidelines will likely be of more use in determining further management.

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET.

OBJECTIVE: Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (Lu-DOTATATE) is a treatment option for patients with well-differentiated metastatic neuroendocrine tumours. Our centre started administering this therapy in 2012. The aim of this study was therefore to analyse the first cohort of patients treated with Lu-DOTATATE to determine its early efficacy and toxicity. PATIENTS AND METHODS: We retrospectively analysed patient, tumour and treatment characteristics, end-of-treatment outcome, time to progression and toxicity in 79 consecutive patients treated with Lu-DOTATATE who had progressive NET according to Response Evaluation Criteria in Solid Tumours criteria. Follow-up time was 12-40 months. Study of Kaplan-Meier plots, analysis of time to progression and multiple regression analysis of factors predictive of time to progression were performed. RESULTS: At end-of-treatment radiological restaging, 13% of patients were found to have partial response and 64% to have stable disease; 23% of patients progressed through treatment. Overall, 47% of patients demonstrated a reduction in chromogranin A levels. The overall estimated median time to progression from the start of treatment was 28 months for the entire cohort and 31, 30 and 5 months for those with partial response, stable disease and progressive disease, respectively. On multivariate regression analysis, higher grade of tumour was found to be significantly associated with shorter progression-free survival. Three patients experienced grade 1 haematotoxicity, five grade 1 nephrotoxicity and one grade 2 nephrotoxicity. CONCLUSION: Early outcomes of patients treated with Lu-DOTATATE are similar to those in previously published series in terms of end-of-treatment efficacy and toxicity. This provides further evidence that this is a safe and efficacious form of treatment for patients with progressive metastatic neuroendocrine tumours.

Patient-specific optimisation of administered activity and acquisition times for 18F-FDG PET imaging.

BACKGROUND: The purpose of this study is to identify a method for optimising the administered activity and acquisition time for 18F-FDG PET imaging, yielding images of consistent quality for patients with varying body sizes and compositions, while limiting radiation doses to patients and staff. Patients referred for FDG scans had bioimpedance measurements. They were injected with 3 MBq/kg of 18F up to 370 MBq and scanned on a Siemens Biograph mCT at 3 or 4 min per bed position. Data were rebinned to simulate 2- and 1-min acquisitions. Subjective assessments of image quality made by an experienced physician were compared with objective measurements based on signal-to-noise ratio and noise equivalent counts (NEC). A target objective measure of image quality was identified. The activity and acquisition time required to achieve this were calculated for each subject. Multiple regression analysis was used to identify expressions for the activity and acquisition time required in terms of easily measurable patient characteristics. RESULTS: One hundred and eleven patients were recruited, and subjective and objective assessments of image quality were compared for 321 full and reduced time scans. NEC-per-metre was identified as the objective measure which best correlated with the subjective assessment (Spearman rank correlation coefficient 0.77) and the best discriminator for images with a subjective assessment of "definitely adequate" (area under the ROC curve 0.94). A target of 37 Mcount/m was identified. Expressions were identified in terms of patient sex, height and weight for the activity and acquisition time required to achieve this target. Including measurements of body composition in these expressions was not useful. Using these expressions would reduce the mean activity administered to this patient group by 66 MBq compared to the current protocol. CONCLUSIONS: Expressions have been identified for the activity and acquisition times required to achieve consistent image quality in FDG imaging with reduced patient and staff doses. These expressions might need to be adapted for other systems and reconstruction protocols.

The Impact of Radiological Response to Peptide Receptor Radionuclide Therapy on Overall Survival in Patients With Metastatic Midgut Neuroendocrine Tumors.

PURPOSE OF THE REPORT: Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced neuroendocrine tumors (NET); however, long-term survival data are scarce. The aim of this study is to determine long-term survival in patients with metastatic midgut NET, according to response to PRRT. PATIENTS AND METHODS: One hundred thirty-three consecutive patients with progressive metastatic midgut NET underwent PRRT. Response at 1 year post PRRT was classified as partial response, stable disease, disease progression, or death. Survival was assessed according to response to PRRT, and predictors of overall survival (OS) and progression-free survival (PFS) were identified. RESULTS: At 1 year post PRRT, 9% had partial response, 50.4% stable disease, 10.5% disease progression, and 30.1% were dead. The OS was 33.5, and PFS was 28.5 months. Predictors of disease progression/death were chromogranin A greater than 10 ULN (OR, 4.6; P = 0.007) and hepatic tumor load greater than 50% (OR, 5; P = 0.004). There was no difference in OS between patients with partial response and those with stable disease post PRRT. In multivariate Cox regression, predictors of OS were number of PRRT cycles (HR, 0.33; P < 0.0005), hepatic tumor load greater than 50% (HR, 3.46; P = 0.01), and outcome at 1 year post PRRT (HR, 21.37; P < 0.0005). Predictors of PFS were number of PRRT cycles (HR, 0.39; P < 0.0005), previous resection of liver metastases (HR, 3.56; P = 0,023), and hepatic tumor load greater than 50% (HR, 3.06; P < 0.0005). CONCLUSIONS: Patients with progressive metastatic midgut NET who achieved stable disease at 1 year post PRRT had similar OS with those with partial response. Hepatic tumor burden was a strong predictor of response to PRRT, PFS, and OS.

Radiation dose of 18F-FDG to lactating breasts, its effect on the effective dose and a more accurate effective dose from 18F-FDG.

INTRODUCTION: Lactating breasts have greater uptake of fluorine-18 fluorodeoxyglucose (F-FDG) than nonlactating breasts; however, there are no published data on the radiation dose from F-FDG to lactating breasts or this effect on the effective dose (ED). In addition, the International Commission on Radiological Protection's (ICRP) most recently published ED of 1.9×10 mSv/MBq from F-FDG was calculated using weighting factors that have since been superseded. We therefore calculated the F-FDG radiation dose to the lactating breast, its effect on the ED and calculated more up-to-date EDs from F-FDG for nonlactating patients. METHODS: Breast uptake of F-FDG and volume were determined from PET/CT images of a lactating patient. These data, together with previously published biokinetic data on F-FDG, were used to calculate a radiation dose to the lactating breasts and its effect on the ED. In addition, tissue weighting factors and organ doses from the ICRP publications 103 and 106 were used to calculate more up-to-date EDs from F-FDG in nonlactating patients. RESULTS: The absorbed dose to the lactating breast from F-FDG is 1.75×10 mGy/MBq, which results in an increase in the ED of 6%. In nonlactating patients, a more up-to-date ED from F-FDG is 1.77×10 mSv/MBq for women and 1.64×10 mSv/MBq for men. CONCLUSION: This is the first reported dosimetry of F-FDG in lactating breasts, data that are required when justifying the radiation dose from an F-FDG PET scan in lactating patients. In addition, we calculated more up-to-date EDs from F-FDG that are lower than the current widely reported ED and should be used in future publications on F-FDG.

Automated quantification with BRASS reduces equivocal reporting of DaTSCAN (123I-FP-CIT) SPECT studies.

BACKGROUND: ¹²³I-FP-CIT (DaTSCAN) SPECT studies of the nigrostriatal pathway are a valuable tool in the diagnosis of movement disorders. However some scans are reported as equivocal with potential adverse consequences. We investigated whether the use of quantification of tracer uptake within the striatum can be used to reduce the number of equivocal reports. MATERIAL AND METHODS: BRASS software (Hermes, Sweden) was used to quantify striatal tracer uptake in DaTSCAN studies of patients referred to our institution. Scans were quantified and numerical limits were determined to distinguish between normal and abnormal scans. Scans were then re-reported both with, and without, the use of quantification. Number of equivocal reports and accuracy of reporting between the two types of reporting were compared. RESULTS: Scan reporting using quantification led to a significant reduction in the number of equivocal reports with no significant change in reporting accuracy. CONCLUSION: Automated quantification of DaTSCAN studies with BRASS and the use of numerical limits can decrease the number of equivocal reports without affecting report accuracy.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography in diagnosis of post-transplant lymphoproliferative disorder.

The aim of the present study was to investigate the role of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the diagnosis of post-transplant lymphoproliferative disorder (PTLD), a serious complication of solid organ and bone marrow transplant. Between January 2004 and January 2012, 40 patients (22 males; median age 52 ± 17.4 years, range 11-77 years) underwent (18)F-FDG PET/CT scans in our department for diagnostic evaluation of PTLD. Twenty-three (57.5%) patients had negative (18)F-FDG PET/CT and 17 (42.5%) had a positive examination. In five patients PET/CT revealed extranodal disease (adrenal, pleural, spleen, liver, lung, esophagus and bone involvement). On the basis of our results, (18)F-FDG PET/CT had a sensitivity of 88.2% (95% confidence interval [CI] 0.62-0.98), a specificity of 91.3% (CI 0.70-0.98), a positive predictive value of 88.2% (CI 0.62-0.98) and a negative predictive value of 91.3% (CI 0.70-0.98). The diagnostic performance of CT in patient-based analysis was: a sensitivity of 87.5% (CI 0.60-0.97), a specificity of 88.8% (CI 0.64-0.98), a positive predictive value of 87.5% (CI 0.60-0.97) and a negative predictive value of 88.8% (CI 0.64-0.98). PET/CT in five cases revealed more findings than CT, upstaging the disease, and revealed three extranodal findings, not visualized in conventional imaging. (18)F-FDG PET/CT plays a significant role in the setting of PTLD diagnosis, demonstrating its high accuracy in detecting PTLD.