Ann-Marie Quigley

Intertumoural variability in functional imaging within patients suffering from neuroendocrine tumours an observational, cross-sectional study

123I mIBG (meta-iodobenzylguanidine) and 111In pentetreotide scintigraphy imaging modalities are useful in demonstrating neuroendocrine tumours. Although 111In pentetreotide is generally held to be a more superior imaging agent than 123I mIBG for neuroendocrine tumours, we noted a differential uptake of the two agents by different tumour sites within individual patients. In some cases, the two tracers appeared to demonstrate different lesions within the same patient. The aim of this study wasto determine the positivity of the two imaging modalities, the degree of correlation between them and to highlight any clinically useful differences between the two modalities. 123I mIBG and 111In pentetreotide images of 149 consecutive, biopsy-proven or biochemically confirmed, neuroendocrine tumour patients were compared. All the patients underwent whole-body imaging and upper abdominal single-photon emission computed tomography (SPECT). The results of both types of imaging were compared, lesion by lesion, for each individual patient. The overall positivity rate for 111In pentetreotide was 79%, and that for 123I mIBG was 63%. When both agents were positive, the 111In pentetreotide highlighted more lesions within the same patient in 33%, whilst the 123I mIBG highlighted more lesions in 13%. In 12% of patients both agents were positive, but different lesions were seen with the two agents. 111In pentetreotide has greater positivity than 123I mIBG for imaging neuroendocrine tumours. However, the two modalities can highlight different tumour lesions, suggesting the presence of phenotypically diverse tumour populations within individual patients. These findings are likely to influence clinical management in the future.

Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) amyloidosis and its relationship with skeletal muscle and soft tissue amyloid

Aims High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR amyloidosis. Methods and results Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A-associated ATTRm (n = 59) amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). Conclusion 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.

The role of 99mTc-depreotide in the management of neuroendocrine tumours

Background111In-pentetreotide scan (OctreoScan) is a widely available agent with high sensitivity for imaging neuroendocrine tumours. Negative 111In-pentetreotide poses diagnostic as well as therapeutic problems in terms of staging and consideration of targeted radionuclide therapy. AimTo assess the role of 99mTc-depreotide in patients with negative or weakly positive OctreoScan (Krenning score≤1; measured on a scale range 0–4). To determine the usefulness of 99mTc-depreotide scintigraphy for highlighting lesions that may be missed by OctreoScan and/or CT/MRI imaging. Study designProspective analysis of 25 patients with neuroendocrine tumours, with negative or weakly positive 111In-pentetreotide scans, who were consecutively enrolled to undergo 111In-pentetreotide and 99mTc-depreotide imaging. The results were compared with either CT or MRI scans. ResultsHistology was available for 20 of 25 patients: of these 40% had high-grade tumours (cellular proliferation marker Ki-67 score >20%), a further 35% had intermediate-grade tumours (Ki-67 2–20%), and the remaining 25% had low-grade tumours (Ki-67 <2%). Fifty-two percent of patients had completely negative and 48% had weakly positive OctreoScan results. Thirty-two percent of these same patients had significantly positive 99mTc-depreotide scans (Krenning score≥2), with the histology demonstrating intermediate-grade or high-grade tumours. Conclusion99mTc-depreotide imaging has low sensitivity but is useful in a one-third of OctreoScan-negative patients, displaying significantly better uptake than 111In-pentetreotide in this patient group. It aids diagnosis by highlighting lesions not seen by OctreoScan and/or CT/MRI imaging, and can possibly identify a group of patients amenable to therapy with radionuclide agents, such as SOM230, targeting somatostatin receptor subtypes 2, 3 and 5.

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.

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.

Early efficacy of and toxicity from lutetium-177-dotatate treatment in patients with progressive metastatic Net

Objective Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (177Lu-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 177Lu-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 177Lu-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 177Lu-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.

Rapid and severe adverse reaction to adenosine during a pharmacological stress test for a myocardial perfusion scan.

To the Editor: We wish to report an atypical and lifethreatening reaction to adenosine in an asthmatic during stressing for a myocardial perfusion scan (MPS). A 55-year-old man with renal failure secondary to diabetes was referred for anMPS. He also had asthma, diagnosed in childhood, for which he took inhaled beclomethasone and prn salbutamol which he used prior to physical exertion, rather than to relieve shortness of breath. He denied ever wheezing, had never been admitted to hospital for asthma, had never smoked, and his asthma was currently stable. Auscultation of his chest did not reveal any wheeze or crepitations. Our guidelines are adapted from the American Society of Nuclear Cardiology guidelines and, as we considered his asthma well controlled, we commenced the stress test with an initial minute of a half ‘‘test’’ dose adenosine infusion. After this test and a further 2 minutes of full-dose infusion, no symptoms were reported. After 2 minutes of the test, the patient reported feeling short of breath. However, he looked well with no wheeze on auscultation; therefore, salbutamol was self-administered and the test was continued. Over the following minute, the patient reported increasing shortness of breath and started to look unwell. The adenosine infusion was therefore stopped; however, from this point he rapidly deteriorated. Despite inhaled salbutamol and high-flow oxygen, his oxygen saturations dropped from 95% to a low of 35%. His heart rate dropped to 35 beats per minute; he lost consciousness but did not have a cardiac or respiratory arrest. Chest auscultation revealed very poor entry bilaterally but no wheeze. He was managed by the cardiac arrest team with high-flow oxygen and airway support. His oxygen saturations recovered over 5 minutes and he regained consciousness after 20Y30 minutes. Aminophylline was not administered as initial management focused on basic resuscitation, and the cardiac arrest team were concerned about the use of aminophylline and the patient’s hypertension (225/80). Following the incident, the contents of the adenosine syringe were rechecked by pharmacy as was the infusion rate. Fortunately, the patient made a complete recovery. Although adenosine-induced bronchospasm is a recognized side effect in patients with asthma, it is not an absolute contraindication and a ‘‘test’’ dose is commonly employed before starting the full dose. This patient appeared to develop a rapid and severe bronchospasm after fully tolerating adenosine for 3 minutes. We are not aware of this type of reaction being reported previously although similar reactions in patients with COPD who have been given dipyridamole have been described. Recent articles reporting on the use of adenosine in patients with asthma did not describe reactions similar to this. Although there is good evidence that the use of adenosine in selected patients with asthma is safe as a pharmacological stressor, this case demonstrates that apparently unpredictable, life-threatening reactions can occur and healthcare professionals involved in myocardial stressing should be aware of this and be competent in the management of adenosine-induced bronchospasm as well as advanced life support.