Repeat Positron Emission Tomography Scan Research Articles

An in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates.

Positron emission tomography (PET) has become an essential clinical tool for diagnosing neurodegenerative diseases with abnormal accumulation of proteins like amyloid-β or tau. Despite many attempts, it has not been possible to develop an appropriate radioligand for imaging aggregated α-synuclein in the brain for diagnosing, e.g., Parkinson’s Disease. Access to a large animal model with α-synuclein pathology would critically enable a more translationally appropriate evaluation of novel radioligands. We here establish a pig model with cerebral injections of α-synuclein preformed fibrils or brain homogenate from postmortem human brain tissue from individuals with Alzheimer’s disease (AD) or dementia with Lewy body (DLB) into the pig’s brain, using minimally invasive surgery and validated against saline injections. In the absence of a suitable α-synuclein radioligand, we validated the model with the unselective amyloid-β tracer [11C]PIB, which has a high affinity for β-sheet structures in aggregates. Gadolinium-enhanced MRI confirmed that the blood-brain barrier was intact. A few hours post-injection, pigs were PET scanned with [11C]PIB. Quantification was done with Logan invasive graphical analysis and simplified reference tissue model 2 using the occipital cortex as a reference region. After the scan, we retrieved the brains to confirm successful injection using autoradiography and immunohistochemistry. We found four times higher [11C]PIB uptake in AD-homogenate-injected regions and two times higher uptake in regions injected with α-synuclein-preformed-fibrils compared to saline. The [11C]PIB uptake was the same in non-injected (occipital cortex, cerebellum) and injected (DLB-homogenate, saline) regions. With its large brain and ability to undergo repeated PET scans as well as neurosurgical procedures, the pig provides a robust, cost-effective, and good translational model for assessment of novel radioligands including, but not limited to, proteinopathies.

Clinical Images: Erdheim-Chester disease.

The patient, a 57-year-old man, presented to the hospital with right-sided pleuritic chest pain, dyspnea on exertion, and lower extremity edema. He was found to have a large pericardial effusion with early tamponade on echocardiography. Pericardiocentesis yielded 900 ml of serosanguineous fluid. Soon after, he developed epigastric pain. A computed tomography scan of the abdomen revealed diffuse inflammation of the retroperitoneal spaces, a rim of attenuation surrounding the aorta (A, short arrows), and a perirenal infiltrative process involving both kidneys and giving a hairy kidney appearance (A, long arrows). The differential diagnosis of a hairy kidney includes lymphoma, sarcoidosis, and Erdheim-Chester disease (ECD) (1). Knowing that ECD can affect long bones, we obtained radiographs of the femur, which revealed diffuse sclerotic foci and mild cortical thickening (B) (2). A biopsy of the femur showed sclerotic bone with histiocytoid marrow infiltrates. Further staining was positive for CD68, lysozyme, and CD163, consistent with ECD. An immunohistochemical stain was positive for BRAF V600E mutation. Vemurafenib was started, and 4 months later, a repeat positron emission tomography scan showed a vast improvement in his disease burden. ECD is a non–Langerhans histiocytic disease that affects multiple body systems. What was once a rare disease is now becoming more frequently identified as we learn more about its histopathology. ECD is of particular interest to rheumatologists because it can mimic large vessel vasculitis given that ECD can present with a thickened or coated aorta. The pathogenesis of ECD is derived from a malignancy of myeloid progenitor cells that undergo a BRAF mutation, which is typically V600E. This mutation makes it amenable to treatment with BRAF kinase inhibitors, such as vemurafenib and dabrafenib. However other treatments, such as interferon-α, interleukin 1 inhibitors, and tumor necrosis factor inhibitors, have been used as well. Author disclosures are available at https://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2Facr2.11392&file=acr211392-sup-0001-Disclosureform.pdf. Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Cerebral Vasculopathy in Sickle Cell Anemia: Diagnostic Contribution of Positron Emission Tomography

AbstractChildren with sickle cell anemia (SS) have an increased risk for cerebral vasculopathy with stroke (CVA) and cognitive impairment. The present study examines the extent to which adding positron emission tomography (PET) to magnetic resonance imaging (MRI) can improve the detection of cerebral vasculopathy. Whereas MRI has been the prime modality for showing anatomical lesions, PET excels at assessing the functional metabolic state through glucose utilization 2-deoxy-2 [18F] fluoro-D-glucose (FDG) and microvascular blood flow ([15O]H2O). Forty-nine SS children were studied. Among them, 19 had clinically overt CVA, 20 had life-threatening hypoxic episodes or soft neurologic signs, and 10 were normal based on neurological history and examination. For the entire sample of 49 subjects, 30 (61%) had abnormal MRI findings, 36 (73%) had abnormal PET findings, and 44 (90%) showed abnormalities on either the MRI or the PET or both. Of the 19 subjects with overt CVA, 17 had abnormal MRI (89%), 17 had abnormal PET (89%), and 19 (100%) had either abnormal MRI or PET or both. Among the 20 subjects with soft neurologic signs, 10 (50%) had abnormal MRI, 13 (65%) had abnormal PET, and 17 (85%) had abnormal MRI and/or PET. Six (60%) of the 10 neurologically normal subjects had abnormal PET. Among the 30 subjects with no overt CVA, 25 (83%) demonstrated imaging abnormalities based on either MRI or PET or both, thus, silent ischemia. Lower than average full-scale intelligence quotient (FSIQ) was associated with either overt CVA or silent ischemic lesions. Four subjects who received chronic red blood cell transfusion showed improved metabolic and perfusion status on repeat PET scans. In conclusion, (1) the addition of PET to MRI identified a much greater proportion of SS children with neuroimaging abnormalities, particularly in those who had no history of overt neurologic events. (2) PET lesions are more extensive, often bihemispheric, as compared with MRI abnormalities. (3) PET may be useful in management as a tool to evaluate metabolic improvement after therapeutic interventions, and (4) the correlation of PET abnormalities to subsequent stroke or progressive neurologic dysfunction requires further study.

S1470 Pruritis as the Presenting Symptom of Double Hit Pancreatic Lymphoma

INTRODUCTION: Obstructive jaundice can be classified as either intraluminal, transmural, or extra luminal. Among extra luminal causes, mass effect from an underlying malignancy is often present. Most often this is the result of a primary pancreatic carcinoma. Rarely, obstruction of the bile duct can be caused by a lymphoma in the pancreatic region. When lymphoma is present, Non-Hodgkin’s Lymphoma (NHL) is most likely, with the most common subtype being diffuse large B-cell lymphoma (DLBCL). Double hit lymphoma (DHL) is an aggressive type of NHL characterized by rearrangements most commonly in the Myc gene and BCL 2 or 6 genes. CASE DESCRIPTION/METHODS: We describe a case of a 58 year old male with a history of hypertension, chronic kidney disease and heart failure, who was evaluated in clinic for a 2 week history of severe pruritis. Liver function tests revealed alkaline phosphatase 913 units per liter (U/L), AST 353 U/L, ALT 570 U/L and total bilirubin 2.32 mg/dL. The patient was admitted for further workup. CT abdomen revealed a 8 × 6 cm mass in the pancreatic head, concerning for primary pancreatic malignancy. He underwent endoscopic retrograde cholangiopancreatography with stent placement in the common bile duct and pancreatic duct as well as a biopsy of the mass. Biopsy revealed abnormal B cell populations consistent with lymphoma. Fluorescence in situ hybridization was performed and showed high grade B cell DHL with MYC gene rearrangement. Positron emission tomography (PET) scan was then performed showing hyper-metabolic matted adenopathy centered in the peripancreatic ligament distribution measuring up to 17.6 SUV, confirming lymphoma. Chemotherapy with rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) was promptly initiated, as well as intrathecal prophylaxis with methotrexate. After completing 5 cycles, a repeat PET scan showed minimal metabolic activity at the known cancer site and no new or progressive findings. DISCUSSION: DHL presenting as pruritus in the setting of obstructive painless jaundice is a very rare entity. Due to the relative infrequency of this presentation, NHL is hardly considered in the initial differential diagnosis for obstructive jaundice. Overall, obstruction caused by lymphoma carries a more favorable prognosis than patients with obstruction from primary pancreatic malignancies. This case highlights the need for thorough evaluation of pruritus as early diagnosis of lymphoma can lead to better patient outcomes.Figure 1.: CT Abdomen with large pancreatic head mass.Figure 2.: Pre and Post Chemotherapy PET CT Scans. Left: Hypermetabolic matted adenopathy centered in the peripancreatic and gastrohepatic ligament distribution concerning for Lymphoma. Right: Stable matted lymphadenopathy in the peripancreatic region with stable generalized low-grade uptake. No new or progressive lymphomatous disease is seen.Figure 3.: Pancreatic Mass Biopsy Histology, PAP stain at 40X. Red arrow - large cells 2-5x the size of a small lymphocyte. Black arrow - lymphocyte with nucleus as large as a histiocyte nucleus.

Study of the Effect of Reconstruction Parameters for Myocardial Perfusion Imaging in PET With a Novel Flow Phantom

Myocardial perfusion imaging (MPI) with positron emission tomography (PET) allows quantitative temporal measurements of the radioactive tracer distribution in tissue. The quantification for myocardial blood flow (MBF) is conducted with kinetic modelling of the image-derived time-activity curves (TACs) allowing derivation for MBF in units of mL/min per gram of tissue. The ordered-subset expectation maximization (OSEM) reconstruction algorithm with time-of-flight (TOF) and point spread function (PSF) modelling is now routinely employed in cardiac imaging. However, the varying counting statistics of the MPI measurements conducted with short-lived tracers present a challenge for the PET image reconstruction methods. Thus, the effect of the reconstruction methods on the flow quantification needs to be evaluated in a standardized manner. Recently, a novel PET flow phantom modelling the MBF has been developed for investigation of the standardization of the MBF measurements. In this study, the effect of the reconstruction parameters on the image-derived flow values against a known reference flow of the flow phantom was studied with [15O]H2O. The effects were studied by comparison of TACs and relative errors of the image-derived flow values with respect to the phantom-derived reference flow value using 5 repeated PET scans with fixed acquisition parameters using a digital Discovery MI PET/CT system. The reconstruction methods applied were OSEM using both TOF and PSF (OSEM-TOF-PSF) with several matrix sizes (128x128, 192x192, 256x256, 384x384), Gaussian filter sizes (4 mm, 8mm) and OSEM without TOF and PSF (OSEM), with TOF (OSEM-TOF) and with PSF (OSEM-PSF) in addition to recently introduced regularized reconstruction method based on Bayesian-penalized maximum likelihood (Q.Clear). Between repeated measurements, the image-derived flow values showed high repeatability with a SD less than 2 mL/min as well as high accuracy with the maximum error of 7 % with respect to the reference flow for all reconstructions. Overall, reconstruction settings had only a small impact on the resulting flow values. In conclusion, due to the small differences detected, any of the implemented reconstruction algorithms on the system can be applied in MPI studies for accurate flow quantification.

INCIDENTAL PULMONARY ADENOCARCINOMA DETECTED ONLY IN ONE EXPLANTED LYMPH NODE OF A LUNG TRANSPLANT RECIPIENT WITH OLIGO-METASTATIC RECURRENCE ONE YEAR AFTER TRANSPLANT

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: The most common indications for lung transplant (LT) in the post-lung allocation score (LAS) era are idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Unexpected neoplasms are detected in between 1-4% of LT recipients upon pathological review of explants. CASE PRESENTATION: We present a rare case of incidental adenocarcinoma of the lung detected only on an explanted lymph node after LT. A 73-year-old man underwent bilateral sequential LT for IPF. Explant pathology revealed a 0.2 cm focus of pulmonary adenocarcinoma in one out of 21 lymph nodes (strongly positive for TTF-1) without a parenchymal primary focus. The explanted lungs were re-reviewed to confirm the absence of a primary focus (pathological stage pT0, pN1). The patient was subsequently followed with serial imaging including computed tomography (CT) and positron emission tomography (PET) scans. One year after LT he suffered a compression fracture at L1 and was hospitalized for hyponatremia. Workup revealed lesions in the T10 vertebra, right second rib and in the left acetabulum that showed mild uptake on PET scans. He underwent a CT-guided biopsy of the acetabular lesion, which was consistent with adenocarcinoma of pulmonary origin (strongly positive for keratin AE1/AE3 and CK7, while focally positive for TTF-1) – all consistent with a diagnosis of oligometastatic disease. His immunosuppression was lowered but given his leucopenia, he was thought to be a poor candidate for systemic therapy. After multidisciplinary discussions with the patient it was decided the best course of action for this patient would be stereotactic body radiation therapy (SBRT). He was treated with one dose of 20Gy radiation to each of the three sites of metastasis. The patient tolerated the treatment well and had no complications. Four months after initial therapy, repeat PET scan revealed a new FDG avid in the left pubic body concerning for metastasis and showed stable uptake in the three previously treated lesions. After additional discussions the patient and medical team again opted for SBRT to the lesion. He underwent single dose 20Gy radiation without complications. The patient tolerated all procedures well and continues to do well post treatment. DISCUSSION: Diagnosis and management of incidental neoplasms post-LT is challenging. This case highlights the importance of in depth pathological evaluation of lung explants and lymph nodes to look for foci of malignancy not detected on prior clinical evaluation. CONCLUSIONS: High clinical suspicion, lowering immunosuppression and multidisciplinary management are key in managing patients with incidental malignancies detected on lung explants. The incidence of such tumors will likely increase given the higher number of LT for IPF in the post-LAS era. Reference #1: Panchabhai TS, Arrossi AV, Patil PD, Bandyopadhyay D, Budev MM, McCurry KR, Farver C. Unexpected Neoplasms in Lungs Explanted From Lung Transplant Recipients: A Single-Center Experience and Review of Literature. Transplant Proc. 2018;50(1):234-240. DISCLOSURES: No relevant relationships by Hesham Abdelrazek, source=Web Response No relevant relationships by Sreeja Biswas Roy, source=Web Response No relevant relationships by Thomas Luzny, source=Web Response No relevant relationships by Tanmay Panchabhai, source=Web Response no disclosure on file for Nitika Thawani; Speaker/Speaker's Bureau relationship with Genentech Please note: $5001 - $20000 Added 03/18/2019 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $5001 - $20000 Added 03/18/2019 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Grifols Please note: $5001 - $20000 Added 03/18/2019 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Shire Please note: $1001 - $5000 Added 03/18/2019 by Rajat Walia, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Astellas Please note: $5001 - $20000 Added 03/18/2019 by Rajat Walia, source=Web Response, value=Honoraria

Quality assessment of positron emission tomography scans: recommendations for future multicentre trials

Background: Standardization protocols and guidelines for positron emission tomography (PET) in multicenter trials are available, despite a large variability in image acquisition and reconstruction parameters exist. In this study, we investigated the compliance of PET scans to the guidelines of the European Association of Nuclear Medicine (EANM). From these results, we provide recommendations for future multicenter studies using PET.Material and methods: Patients included in a multicenter randomized phase II study had repeated PET scans for early response assessment. Relevant acquisition and reconstruction parameters were extracted from the digital imaging and communications in medicine (DICOM) header of the images. The PET image parameters were compared to the guidelines of the EANM for tumor imaging version 1.0 recommended parameters.Results: From the 223 included patients, 167 baseline scans and 118 response scans were available from 15 hospitals. Scans of 19% of the patients had an uptake time that fulfilled the Uniform Protocols for Imaging in Clinical Trials response assessment criteria. The average quality score over all hospitals was 69%. Scans with a non-compliant uptake time had a larger standard deviation of the mean standardized uptake value (SUVmean) of the liver than scans with compliant uptake times.Conclusions: Although a standardization protocol was agreed on, there was a large variability in imaging parameters. For future, multicenter studies including PET imaging a prospective central quality review during patient inclusion is needed to improve compliance with image standardization protocols as defined by EANM.

Estimation of noise-free variance to measure heterogeneity.

Variance is a statistical parameter used to characterize heterogeneity or variability in data sets. However, measurements commonly include noise, as random errors superimposed to the actual value, which may substantially increase the variance compared to a noise-free data set. Our aim was to develop and validate a method to estimate noise-free spatial heterogeneity of pulmonary perfusion using dynamic positron emission tomography (PET) scans. On theoretical grounds, we demonstrate a linear relationship between the total variance of a data set derived from averages of n multiple measurements, and the reciprocal of n. Using multiple measurements with varying n yields estimates of the linear relationship including the noise-free variance as the constant parameter. In PET images, n is proportional to the number of registered decay events, and the variance of the image is typically normalized by the square of its mean value yielding a coefficient of variation squared (CV 2). The method was evaluated with a Jaszczak phantom as reference spatial heterogeneity (CVr 2) for comparison with our estimate of noise-free or ‘true’ heterogeneity (CV t 2). We found that CV t 2 was only 5.4% higher than CV r 2. Additional evaluations were conducted on 38 PET scans of pulmonary perfusion using 13NN-saline injection. The mean CV t 2 was 0.10 (range: 0.03–0.30), while the mean CV 2 including noise was 0.24 (range: 0.10–0.59). CV t 2 was in average 41.5% of the CV 2 measured including noise (range: 17.8–71.2%). The reproducibility of CV t 2 was evaluated using three repeated PET scans from five subjects. Individual CV t 2 were within 16% of each subject's mean and paired t-tests revealed no difference among the results from the three consecutive PET scans. In conclusion, our method provides reliable noise-free estimates of CV t 2 in PET scans, and may be useful for similar statistical problems in experimental data.

Reproducibility of Non-Invasive A1 Adenosine Receptor Quantification in the Rat Brain Using [18F]CPFPX and Positron Emission Tomography

The A1AR antagonist 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([(18)F]CPFPX) has recently been shown to be a suitable radiotracer for quantitative in vivo imaging of the A1 adenosine receptor (A1AR) in rats. The present study evaluates the reproducibility of non-invasive longitudinal A1AR studies with [(18)F]CPFPX and a dedicated small animal positron emission tomography (PET) scanner. Twelve male Sprague Dawley rats underwent four repeated dynamic PET scans with a bolus injection of [(18)F]CPFPX. A1AR availability was determined by different non-invasive approaches including simplified and multilinear reference tissue (olfactory bulb)-based models and graphical methods. The outcome parameter binding potential (BP) was evaluated in terms of variability and reproducibility. Repeated estimations of [(18)F]CPFPX BP ND gave reliable results with acceptable variability (mean 12%) and reproducibility (intraclass correlation coefficients raging from 0.57 to 0.68) in cortical and subcortical regions of the rat brain. With regard to kinetic models, test-retest stability of the simplified reference-tissue model (SRTM) was superior to multilinear and graphical approaches. Non-invasive quantification of A1AR density in the rat brain is reproducible and reliable with [(18)F]CPFPX PET and allows longitudinal designs of in vivo imaging studies in rodents.

Ofatumumab (OFA) in Combination with CHOP for Previously Untreated Follicular Lymphoma: Follow-up Results

AbstractAbstract 1632 Background:OFA is a fully human monoclonal antibody that binds to both the large and small extracellular loops of CD20. OFA is currently approved for patients (pts) with refractory chronic lymphocytic leukemia and has demonstrated activity in non-Hodgkin's lymphomas, including follicular lymphoma (FL). We previously reported results of a phase II study of OFA in combination with CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg daily for 5 days) chemotherapy (O-CHOP) in pts with previously untreated FL (Czuczman et al. Br J Haematol. 2012;157:438). We now report updated efficacy, safety and pharmacokinetic (PK) follow-up data for this study. This trial is registered at www.clinicaltrials.gov (NCT00494780). Methods:Fifty-nine pts with previously untreated FL were randomized to OFA 500 mg (n = 29) or 1000 mg (n = 30) on day 1, with CHOP on day 3, every 3 weeks for 6 cycles. The primary end point was overall response rate (ORR), as assessed by an independent end points review committee. Secondary end points included complete response (CR), progression-free survival (PFS), overall survival, adverse events (AEs) and PK. Follow-up assessments after therapy were done every 3 months (mo) until mo 12 and then every 6 mo until alternative FL therapy or mo 60. Positron emission tomography (PET) was done at baseline and 3 mo after last therapy. Blood samples for PK analyses were collected to determine OFA serum concentrations, and noncompartmental methods were used to estimate PK parameter values. Results:Fifty-eight pts received therapy; 1 pt in the 1000-mg group withdrew before initiation of therapy. The ORR was 90% for the 500-mg group (n=29) and 100% for the 1000-mg group (n=29); 55% of pts achieved CR or unconfirmed CR (CRu), including 67% of pts with a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3–5. At baseline, 57 pts were PET positive, and 49 pts underwent repeat PET scans after therapy. Forty of 49 pts (82%) became PET negative, including 27 of 29 (93%) pts who achieved CR/CRu and 13 of 20 pts (65%) who achieved partial response (PR). With a median follow-up of 33.8 mo, the median PFS for the 500-mg group was 27.6 mo and the median PFS for the 1000-mg group was not reached (P=0.46). Median PFS for pts with FLIPI scores of 0–1 (n=17), 2 (n=20) and 3–5 (n=21) was not reached, 27.6 mo and 27.6 mo, respectively (P=0.68). Median PFS for pts (n=32) who achieved CR/CRu was also not reached and was 28.3 mo for pts (n=23) achieving PR. Median PFS for PR pts who were PET positive and PET negative after therapy was not reached and 28.3 mo, respectively. No deaths have been reported. No hematologic serious AEs (SAEs) were experienced during the follow-up period. During the follow-up period, non-hematologic SAEs were reported in 1 pt in the 500-mg group (pneumonia) and 5 pts in the 1000-mg group (abdominal hernia, erysipelas, intervertebral disc protrusion, meniscus lesion and vulval cancer); none were ofatumumab-related. After repeated dosing, OFA clearance values were 6.3 and 5.9 mL/h, and half-life values were 27.2 and 26.8 days in the 500-mg and 1000-mg groups, respectively. Conclusions:O-CHOP achieved durable remissions in previously untreated pts with FL. There were no observed PK or PFS differences between the 500-mg and 1000-mg arms, but the study was not powered to detect such differences. O-CHOP was effective in pts with high-risk FLIPI scores, and CR/CRu and PFS rates were not affected by FLIPI score. PET status after therapy did not predict PFS in responding pts, although the study was too small to make such a determination. These results indicate that O-CHOP should be studied as a therapy for FL pts with high-risk FLIPI scores. [Display omitted] Disclosures:Czuczman:GlaxoSmithKline: Advisory board Other, Honoraria. Off Label Use: Ofatumumab in follicular lymphoma. Belada:GlaxoSmithKline: Research Funding. Mayer:Roche: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding. Gupta:GlaxoSmithKline: Employment. Lin:GlaxoSmithKline: Employment, Equity Ownership. Winter:GlaxoSmithKline: Employment, Equity Ownership. Goldstein:GlaxoSmithKline: Employment, Equity Ownership. Jewell:GlaxoSmithKline: Employment, Equity Ownership. Lisby:Genmab: Employment, Equity Ownership.

PET hypoxia imaging with FAZA: reproducibility at baseline and during fractionated radiotherapy in tumour-bearing mice

Tumour hypoxia is linked to treatment resistance. Positron emission tomography (PET) using hypoxia tracers such as fluoroazomycin arabinoside (FAZA) may allow identification of patients with hypoxic tumours and the monitoring of the efficacy of hypoxia-targeting treatment. Since hypoxia PET is characterized by poor image contrast, and tumour hypoxia undergoes spontaneous changes and is affected by therapy, it remains unclear to what extent PET scans are reproducible. Tumour-bearing mice are valuable in the validation of hypoxia PET, but identification of a reliable reference tissue value (blood sample or image-derived muscle value) for repeated scans may be difficult due to the small size of the animal or absence of anatomical information (pure PET). Here tumour hypoxia was monitored over time using repeated PET scans in individual tumour-bearing mice before and during fractionated radiotherapy. Mice bearing human SiHa cervix tumour xenografts underwent a PET scan 3 h following injection of FAZA on two consecutive days before initiation of treatment (baseline) and again following irradiation with four and ten fractions of 2.5 Gy. On the last scan day, mice were given an intraperitoneal injection of pimonidazole (hypoxia marker), tumours were collected and the intratumoral distribution of FAZA (autoradiography) and hypoxia (pimonidazole immunohistology) were determined in cryosections. Tissue section analysis revealed that the intratumoral distribution of FAZA was strongly correlated with the regional density of hypoxic (pimonidazole-positive) cells, even when necrosis was present, suggesting that FAZA PET provides a reliable measure of tumour hypoxia at the time of the scan. PET-based quantification of tumour tracer uptake relative to injected dose showed excellent reproducibility at baseline, whereas normalization using an image-derived nonhypoxic reference tissue (muscle) proved highly unreliable since a valid and reliable reference value could not be determined. The intratumoral distribution of tracer was stable at baseline as shown by a voxel-by-voxel comparison of the two scans (R = 0.82, range 0.72-0.90). During treatment, overall tracer retention changed in individual mice, but there was no evidence of general reoxygenation. Hypoxia PET scans are quantitatively correct and highly reproducible in tumour-bearing mice. Preclinical hypoxia PET is therefore a valuable and reliable tool for the development of strategies that target or modify hypoxia.

Change in maximum standardized uptake value on repeat positron emission tomography after chemoradiotherapy in patients with esophageal cancer identifies complete responders

The objective was to identify whether repeat positron emission tomography scan after neoadjuvant chemoradiotherapy in patients with esophageal cancer predicted a complete response. A retrospective study using a prospective database was performed. Patients had esophageal cancer and underwent neoadjuvant chemoradiotherapy, an initial and repeat positron emission tomography, endoscopic ultrasound with fine-needle aspiration (at the same institution), and Ivor Lewis esophagogastrectomy with lymph node resection. There were 221 patients who underwent Ivor Lewis, 86 of whom had their initial and repeat positron emission tomography scans performed at the same center. Of these, 37 patients (43%) were complete responders. The median maximum standardized uptake value of esophageal cancer decreased by 72% in the 37 patients who were complete responders, by 58% in the 31 patients who were partial responders, and by 37% in the 18 patients who had a minimal pathologic response. When the maximum standardized uptake value decreased by more than 64%, the patient was likely to be a complete responder (P = .003, area under the curve = 0.75). When initial and repeat positron emission tomography scans are performed at the same center at least 30 days after the completion of preoperative chemoradiotherapy, the percent change in the maximum standardized uptake value is a predictor of the response to chemoradiotherapy by a patient with esophageal cancer. When the maximum standardized uptake value decreases by 64% or more, it is likely that the patient is a complete responder. These data may help guide neoadjuvant therapy and identify patients for a future randomized study that compares observation with surgical resection in patients with esophageal cancer who appear to be complete responders.

18FDG‐PET IMAGING IN CANINE LYMPHOMA AND CUTANEOUS MAST CELL TUMOR

Positron Emission Tomography (PET) using the glucose analog 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) is a common imaging modality for diagnosis and management of many human malignancies. We evaluated 18FDG-PET in dogs with either multicentric lymphoma (LSA) or cutaneous mast cell tumor (MCT). A prototype large field-of-view PET scanner was used to collect whole-body images in nine dogs with LSA or MCT. Both tumors were characterized by avidity for 18FDG. In dogs with LSA, 18FDG-PET correctly identified involvement of superficial and internal lymph nodes, liver, and spleen. Repeated PET scans after induction chemotherapy demonstrated resolution of abnormal 18FDG uptake within these sites. In dogs with MCT, 18FDG-PET correctly identified MCT metastasis to regional lymph nodes in all dogs in which this was suspected or confirmed with cytology or biopsy before the PET scan. In two dogs, additional sites of mast cell disease were identified with 18FDG-PET that were undetected on physical examination and/or regional lymph node cytology. 18FDG-PET holds promise as a whole-body staging method for canine LSA and MCT.

A novel approach for reduction of brown fat uptake on FDG PET

The aim of this study was to determine whether or not a single dose of a beta-blocker, such as propranolol 40 mg, administered 60 min prior to (18)F-fluorodeoxyglucose ((18)F-FDG) injection would help reduce brown fat uptake of (18)F-FDG. Patients who were referred for either a pre-treatment or a post-treatment evaluation positron emission tomography (PET) scan and who showed (18)F-FDG uptake in brown adipose tissue (BAT) were included in this study. The total number of patients who showed uptake in BAT and in whom a repeat study was carried out after propranolol injection was 40. A repeat PET scan was carried out after an interval of at least 48 h. Propranolol at a dose of 40 mg was given orally 60 min prior to the (18)F-FDG injection. A whole-body PET scan was performed on a dedicated whole-body PET scanner (ADVANCE, GE Medical Systems, Milwaukee, WI), using attenuation correction with 68-Ge external pin sources. We observed that (18)F-FDG uptake in BAT was absent in 36 (90%) patients post propranolol. We conclude that propranolol reduces the uptake of (18)F-FDG in BAT, and thus improves the accuracy of PET imaging.

Focal F-18 Fluoro-Deoxy-Glucose Accumulation in the Lung Parenchyma in the Absence of CT Abnormality in PET/CT

To demonstrate 3 cases of artifactual focal F-18 fluoro-deoxy-glucose accumulation in the lung parenchyma in the absence of any computed tomographic (CT) abnormality. Three patients were examined: a 30-year-old man who had a positron emission tomography (PET)/computed tomography for restaging a biopsy-proven recurrence of head and neck cancer, a 68-year-old woman who was referred for initial staging of esophageal carcinoma, and a 57-year-old man who had a PET/computed tomography for initial staging of melanoma. In each case, there was intense focal activity in the lung parenchyma with no corresponding CT abnormality. Each patient was further evaluated with a repeat PET scan in days 1 and 3 in the first 2 cases and with a delayed repeat acquisition in the third case. Patients were followed for 24, 10, and 1 month, respectively. In the first 2 cases, the abnormal focal activity in the lungs had resolved in the repeat study. In the third case, the focus of increased activity in the lung had moved more peripherally in the delayed acquisition. Clinical follow-up was negative for disease in the corresponding pulmonary parenchymal sites. The finding of significant focal accumulation of fluoro-deoxy-glucose in the lung parenchyma in the absence of corresponding CT abnormality was artifactual. This was likely due to injection technique and the creation of particulate embolus. Positron emission tomography/Computed tomographic readers should be aware of this type of artifact to avoid misinterpretation.

A Bayesian Approach to a Patient With a Residual Mass After Treatment for Non-Hodgkin's Lymphoma of the Thyroid

A 51-year-old female with a previous history of Hashimoto’s disease presented with a right neck mass. The mass was thought to involve the thyroid gland. An initial fine needle aspirate was nondiagnostic, but suspicious for lymphoma. An open incisional biopsy of the thyroid mass revealed a diffuse large B-cell lymphoma and surrounding thyroid parenchyma revealing chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis). The large neoplastic lymphoid cells were strongly CD 20 positive on immunohistochemical staining. Flow cytometry revealed that 15% of the cells were abnormal B-lymphocytes with CD 19, CD20, FMC7 expression and loss of immunoglobulin lightchain expression, consistent with a B-cell lymphoma. A computed tomography scan revealed a 3 5 cm mass that involved the thyroid as well as a 1 2 cm right supraclavicular node. A staging work-up, including a positron emission tomography (PET) scan and a bone marrow biopsy, determined that she apparently had disease localized to the neck, with only the thyroid mass and the supraclavicular node demonstrating fluorodeoxyglucose (FDG) uptake. She was treated with four cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, followed by involved-field radiation to the neck (41.40 Gy). After completion of this therapy, a firm, nontender 1.5 cm mass was still present in the right thyroid region. A repeat PET scan, performed approximately 6 weeks after the completion of the radiation, demonstrated that the thyroid mass had shrunk from 5 cm to 1.5 cm and that the supraclavicular node had disappeared. The thyroid mass was still avid for FDG uptake; no other areas of abnormality were noted. A presumptive diagnosis of residual lymphoma was made and the patient was scheduled to be admitted for reinduction chemotherapy to be followed by high-dose chemotherapy with autologous stem-cell support.

In Vivo PET Measurements with [11C]PE2I to Evaluate Fetal Mesencephalic Transplantations to Unilateral 6-OHDA-Lesioned Rats

Positron emission tomography (PET) is a useful tool to assess and visualize neurotransmissions in vivo. In this study, we performed repeated PET scans with [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of the expression of dopamine (DA) transmission component after a fetal mesencephalic transplantation. The fetal mesencephalic cells were transplanted into the striatum of unilateral 6-OHDA-lesioned rats. PET scans with [11C]PE2I were performed to evaluate the DA transporter before and 2 and 4 weeks after the transplantation. Rotation behavior tests, in vitro autoradiography, measurements of DA contents in the striatum by high-performance liquid chromatography (HPLC), and tyrosine hydroxylase (TH) immunohistological examinations were performed at the same time points and examined for their relationship to changes in the dopamine transporter. The number of ipsilateral rotations induced by methamphetamine injections decreased. DA contents in the striatum measured with HPLC significantly increased. In the PET study, the binding potential of [11C]PE2I increased at 4 weeks. The results of the in vitro autoradiography study corresponded with those of the PET study. The degrees of the change in the binding potentials correlated with those of the numbers of rotations in the behavioral study and the DA contents in the striatum. In the histological examination, TH-positive cells with axons were observed at 2 and 4 weeks after the transplantation. As the dopamine transporter exists only in the axon terminal of DA neurons, these results suggested that PET measurements of [11C]PE2I binding indicated not only survival, but maturity and functioning of the transplanted cells. Repeated PET measurements of DA transporters are a useful tool in assessing the effectiveness of neural transplantations.

Detection of Recurrent Cervical Cancer by Whole-Body FDG PET Scan in Asymptomatic and Symptomatic Women

The authors reviewed the medical records of 44 patients who had been previously treated for cervical carcinoma. In these women, a total of 47 examinations with whole-body [18F]fluoro-2-deoxyglucose (FDG) positron emissiontomography (PET) scans were performed to detect recurrent disease. Twenty-one PET scans were performed in women who had symptoms of recurrence and 26 were in asymptomatic women. In the surveillance group, the time to posttreatment PET scans ranged from 2 to 40 months. In symptomatic women, posttreatment scans were performed from 3 to 80 months after treatment (P = 0.02 for difference). Recurrent disease was detected in 8 (30.8%) asymptomatic and 14 (66.7%) symptomatic patients (P = 0.01). Two asymptomatic women had false-negative PET scans. One patient, whose scan was negative for the presence of disease 3 months after treatment, had persistent disease detected in a cervical biopsy taken at the same time. Another developed a recurrence 4 months after a negative PET scan. A diagnosis of recurrent disease 13 months after a negative scan was not considered a false-negative. The sensitivity of PET scan for detection of recurrent disease among asymptomatic patients was 80.0%, specificity was 100%, positive predictive value was 100%, and negative predictive value was 88.9%. There were 15 positive PET scans reported among symptomatic women. Fourteen of these were confirmed by biopsy or computed tomography (CT), but no disease was found in 1 patient whose PET scan indicated vaginal recurrence. Repeat PET scan at 4 months was negative for disease. Another patient had a pelvic mass detected by PET scan and CT, but because it did not appear to exceed surrounding areas in the FDG uptake, she was not considered positive for recurrence. She was found to have adherent bowel at laparotomy and had no evidence of recurrent disease. All negative findings by PET scan in symptomatic women were confirmed by clinical examination, biopsy, or CT. The sensitivity of PET scan for detection of recurrent disease in symptomatic patients was 100%, specificity was 85.7%, positive predictive value was 93.3%, and negative predictive value was 100%.

Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut

Increased, non-pathological FDG uptake in myocardium, stomach and bowel is frequently observed while performing clinical positron emission tomography (PET) studies. This "physiological" increased FDG uptake is not related to (oncological) disease and is unwanted since it may interfere with correct image reading. We evaluated the role of several patient-related factors that may have an influence on this phenomenon. One hundred and seventy-five non-diabetic patients with malignant diseases, referred to our department for routine whole-body FDG-PET, were retrospectively evaluated. Age, blood glucose levels and duration of the fasting period were recorded. FDG uptake in myocardium, bowel and stomach was visually graded. Statistical analysis showed that increased FDG uptake in myocardium, bowel and stomach was not significantly correlated to blood glucose level, age or duration of fasting. Most patients who underwent repeated PET scans (92 scans in 25 patients), showed no or minor changes in uptake in bowel and stomach on the consecutive scans, while myocardial uptake was more variable. Age, fasting period and blood glucose levels did not influence physiological uptake. However, there seemed to be a patient-specific pattern for stomach and bowel uptake.

Assessment of tumor burden and treatment response by 18F-fluorodeoxyglucose injection and positron emission tomography in patients with cutaneous T- and B-cell lymphomas

18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a unique functional/metabolic imaging modality that is efficacious in nodal staging and detection of extranodal involvement for a variety of lymphomas. We report its novel use in evaluating tumor burden and response to therapy in two patients with cutaneous lymphomas. A 24-year-old woman with aggressive subcutaneous panniculitic T-cell lymphoma associated with fever, arthralgias, lymphadenopathy, mild anemia, and widespread painful lesions refractory to multiple treatment strategies exhibited intense uptake of a glucose analogue at sites of clinically apparent (and clinically imperceptible) disease. Denileukin diftitox therapy resulted in clinical remission, and a repeat PET scan failed to detect residual foci of malignancy. A 38-year-old man with a more indolent multifocal primary cutaneous follicle center B-cell lymphoma characterized by few systemic symptoms and slowly evolving lesions demonstrated only mild glucose analogue uptake at sites of disease. Remission was achieved by radiotherapy and intravenous rituximab, and confirmed by a repeat PET scan. Extracutaneous disease was not evident in either patient by this technique. These preliminary data suggest that FDG-PET may be useful in determining disease activity at the time of initial diagnosis, after treatment, and evaluating a suspected recurrence. (J Am Acad Dermatol 2002;47:623-8.)J Am Acad Dermatol 2002;47:623-8.