Michael O'Doherty

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out, interpret, and document quantitative FDG PET/CT examinations, but will concentrate on the optimisation of diagnostic quality and quantitative information.

Role of Imaging in the Staging and Response Assessment of Lymphoma: Consensus of the International Conference on Malignant Lymphomas Imaging Working Group

PURPOSE Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET)–computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely. METHODS An imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research in progress, and identify key areas for research pertaining to imaging and lymphoma. RESULTS A working paper was circulated for comment and presented at the Fourth International Workshop on PET in Lymphoma in Menton, France, and the 12th ICML in Lugano, Switzerland, to update the International Harmonisation Project guidance regarding PET. Recommendations were made to optimize the use of PET-CT in staging and response assessment of lymphoma, including qualitative and quantitative methods. CONCLUSION This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.

99tcm sestamibi — a new agent for parathyroid imaging

Parathyroid imaging using 99Tcm sestamibi has been carried out prior to surgery in five patients with hyperparathyroidism and the results compared with a standard preoperative localization technique using 201T1 (thallous chloride). The 99Tcm sestamibi correctly localized all abnormal glands and showed higher parathyroid to thyroid uptake in three of four parathyroid adenomas. Both agents showed localization in a thyroid adenoma. The higher uptake of sestamibi and better imaging properties of its 99Tcm radiolabel means that the agent may replace thallium for routine preoperative parathyroid localization.

18-FDG-PET as a Prognostic Indicator in the Treatment of Aggressive Non-Hodgkin's Lymphoma-Comparison with CT

Less than 50%, of newly diagnosed patients with aggressive histology Non-Hodgkins Lymphoma (NHL) are cured with standard treatment. The ability to accurately monitor response to treatment is crucial in order to select out patients who need more intensive or salvage treatment. This study assesses the accuracy of FDG-PET as compared to CT in remission assessment following treatment of aggressive NHL, and its value in estimating relapse-free survival. It also evaluates the prognostic value of early interim PET scan in prediction of treatment outcome. Forty-nine adult patients with biopsy-proven aggressive NHL between September 1993 and December 1997 were included. All patients had pre-treatment FDG-PET demonstrating increased uptake in sites of disease. Forty-five patients had a post-treatment PET to assess remission status and 4 had an interim but not a post-treatment PET. Thirty-three of these patients also had a pre- and a post-treatment CT scan. Twenty-three of the 49 patients had an interim PET during chemotherapy to assess early response. PET and CT scan results were correlated with relapse data to examine their accuracy in remission assessment and prediction of prognosis. The median follow-up duration is 30 months. Overall the result of post-treatment PET scan appears to predict diseasc outcome, with relapse rates of 100% (919) and 17% (6/36) for positive and negative PET respectively [p<0.001]. In a subgroup of 33 patients, direct comparison of post-treatment PET and CT shows that PET was more accurate than CT in assessing remission status following treatment. Relapse rate was 100% for positive PET and only 18% for negative PET (p<0.001). compared to 41% and 25%. for patients with positive and negative CT respectively (p<0.1). PET was particularly useful in assessment of residual masses seen on CT scan. The interim PET provided valuable information regarding early assessment of response and long-term prognosis, with no relapses in patients with no or minimal residual uptake compared to 87.5% relapse rate in patients with persistent PET activity (p<0.001). FDG-PET is an accurate method of assessing remission and estimating prognosis following treatment of aggressive NHL, with positive and negative predictive accuracies of 100% and 82% respectively. PET is more accurate than CT in assessing remission and prediction of relapse-free survival. An interim PET scan after 2-3 cycles of chemotherapy predicts the long-term outcome early-on and has a high negative predictive value (100%). This may assist to separate at an early stage good-prognosis patients who are likely to be cured with standard chemotherapy from those patients with poorer prognosis who require alternative treatment.

Results of a Trial of PET-Directed Therapy for Early-Stage Hodgkin’s Lymphoma

BACKGROUND It is unclear whether patients with early-stage Hodgkins lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy. METHODS Patients with newly diagnosed stage IA or stage IIA Hodgkins lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group. RESULTS A total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkins lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkins lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of -3.8 percentage points (95% CI, -8.8 to 1.3). CONCLUSIONS The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkins lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. (Funded by Leukaemia and Lymphoma Research and others; RAPID ClinicalTrials.gov number, NCT00943423.).

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma

PurposeTo determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between ‘core’ laboratories operating in different countries.MethodsFour centres reported scans from 50 patients with stage II–IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using ‘normal’ mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading).ResultsThere was agreement that the response scan was ‘positive’ or ‘negative’ for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74–0.96) for conservative reading and 0.79 (95% CI 0.67–0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively.ConclusionThe criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.

Evaluation of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1

OBJECTIVES The ability of 18fluorodeoxyglucose positron emission tomography (18FDG PET) to detect malignant change in plexiform neurofibromas from patients with neurofibromatosis 1 (NF1) was evaluated. METHODS Eighteen NF1 patients who presented with pain, increase in size, or neurological deficit associated with a plexiform neurofibroma were assessed. Magnetic resonance imaging determined the site and extent of the lesion. Qualitative18FDG PET was performed and the standard uptake value (SUV) measured the regional glucose metabolism. Histological confirmation of the diagnosis was obtained in 10 patients. RESULTS Twenty three plexiform neurofibromas were detected in 18 patients. Seven malignant peripheral nerve sheath tumours, four high grade and three low grade tumours, occurred in five patients. In one patient the clinical and radiological characteristics of the tumour suggested malignancy, but histology was inconclusive. Fifteen benign plexiform neurofibromas were identified in 12 patients and these findings were confirmed histologically in five lesions from four patients. Ten plexiform neurofibromas occurring in eight patients were considered benign on18FDG PET and the patients did not undergo surgery. They remained stable or their symptoms improved on clinical follow up (median 9 months). The results of qualitative 18FDG PET were interpreted as indicating that 13 plexiform neurofibromas were benign and 10 were malignant. No malignant tumours were classified as benign, but two benign tumours were reported as malignant. The SUV was calculated for 20 tumours and was significantly higher in five malignant tumours 5.4 (SD 2.4), than in 15 benign tumours 1.54 (SD 0.7), p=0.002. There was an overlap between benign and malignant tumours in the SUV range 2.7–3.3. CONCLUSIONS 18FDG PET is helpful in determining malignant change in plexiform neurofibromas in NF1. Increased separation between benign and malignant lesions could be obtained by calculating the SUV at about 200 minutes after injection of 18FDG, when the peak activity concentration is obtained in malignant tumours.

[18F]Fluorodeoxyglucose positron emission tomography and its prognostic value in lung cancer

OBJECTIVE Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [(18)F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. METHODS We have retrospectively analyzed 77 patients (mean age, 63. 0 years; male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patients clinical outcome. RESULTS A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6-85.5) for SUV<10; 67.5% (29.0-88.2) for SUV 10-<12; 63.6% (29.7-84.5) for SUV 12-<15; 66.7% (19.5-90.4) for SUV 15-<20; 16.7% (0.01-0.52) for SUV>20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. CONCLUSION We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion.

2009 EANM parathyroid guidelines

The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism.

Quantification of absolute myocardial perfusion in patients with coronary artery disease: comparison between cardiovascular magnetic resonance and positron emission tomography

OBJECTIVES The aim of this study was to compare fully quantitative cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) myocardial perfusion and myocardial perfusion reserve (MPR) measurements in patients with coronary artery disease (CAD). BACKGROUND Absolute quantification of myocardial perfusion and MPR with PET have proven diagnostic and prognostic roles in patients with CAD. Quantitative CMR perfusion imaging has been established more recently and has been validated against PET in normal hearts. However, there are no studies comparing fully quantitative CMR against PET perfusion imaging in patients with CAD. METHODS Forty-one patients with known or suspected CAD prospectively underwent quantitative (13)N-ammonia PET and CMR perfusion imaging before coronary angiography. RESULTS The CMR-derived MPR (MPR(CMR)) correlated well with PET-derived measurements (MPR(PET)) (r = 0.75, p < 0.0001). MPR(CMR) and MPR(PET) for the 2 lowest scoring segments in each coronary territory also correlated strongly (r = 0.79, p < 0.0001). Absolute CMR perfusion values correlated significantly, but weakly, with PET values both at rest (r = 0.32; p = 0.002) and during stress (r = 0.37; p < 0.0001). Area under the receiver-operating characteristic curve for MPR(PET) to detect significant CAD was 0.83 (95% confidence interval: 0.73 to 0.94) and for MPR(CMR) was 0.83 (95% confidence interval: 0.74 to 0.92). An MPR(PET) ≤1.44 predicted significant CAD with 82% sensitivity and 87% specificity, and MPR(CMR) ≤1.45 predicted significant CAD with 82% sensitivity and 81% specificity. CONCLUSIONS There is good correlation between MPR(CMR) and MPR(PET.) For the detection of significant CAD, MPR(PET) and MPR(CMR) seem comparable and very accurate. However, absolute perfusion values from PET and CMR are only weakly correlated; therefore, although quantitative CMR is clinically useful, further refinements are still required.