Yttrium-90 ibritumomab tiuxetan followed by rituximab maintenance as treatment for patients with diffuse large B-cell lymphoma are not candidates for autologous stem cell transplant.

BACKGROUND: Not all patients with diffuse large B-cell lymphoma (DLBCL) are candidates for aggressive regimens. (90)Y ibritumomab tiuxetan ((90)Y-IT), an anti-CD20 radionuclide-conjugated antibody, has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile. METHODS: This phase II trial investigated the overall response rate (ORR), event-free survival (EFS), overall survival (OS) and toxicity of treatment with (90)Y-IT (0.4 or 0.3 mCi (90)Y/kg based on platelets) followed by rituximab maintenance therapy in patients with DLBCL not candidates for transplant. RESULTS: 25 patients were enrolled. At best response 8 patients obtained a complete response (CR) and 1 a partial response (ORR 36%). Median EFS was 2.5 months and OS 8.1 months. No patient who obtained CR later relapsed systemically. Two patients were free of disease at the 61- and 100-month follow-ups; 65% had grade 3/4 thrombocytopenia, but no significant bleeding was observed. Grade 3 nonhematologic toxicity occurred in 36%. Patients who had progressed through a rituximab-containing regimen responded poorly. CONCLUSION: The ORR of 36% with (90)Y-IT as salvage therapy for DLBCL while inferior to more aggressive regimens is significant with acceptable toxicity. For a subset of patients not candidates for salvage with autologous transplant, this treatment strategy can produce a durable, long-lasting remission.

A 48-Year-Old Man With a Hip Fracture and Skin Rash: A Case Report.

Background/Objective: Patients with systemic mastocytosis are at high risk of developing osteoporosis and fractures. Herein, we report a case of hip fragility fracture in a patient with indolent systemic mastocytosis and normal bone density. Case Report: A 48-year-old man experienced a left femoral neck fracture after a fall. After a dose of oxycodone/hydromorphone postoperatively, he developed an anaphylactic reaction. Previously, he experienced a few other episodes of flushing, dizziness, and syncope precipitated by stress and alcohol. His examination was notable for pink and brown macules on his chest, back, arms, and legs. His laboratory test revealed a markedly elevated tryptase level of 171 ng/mL (<11 ng/mL). Treatment including cetirizine, montelukast, and ranitidine controlled his symptoms. His bone density test result was normal. Ten months after hip surgery, his c-terminal telopeptide of collagen type 1 and bone-specific alkaline phosphatase levels significantly increased. The bone scan demonstrated diffusely increased radiotracer uptake throughout the osseous structures. Given high bone turnover and the prior hip fracture, he received zoledronic acid yearly for 3 years, and no further fractures have occurred. Discussion: The case is unusual as the fracture occurred despite normal bone density and significant osteosclerosis, which was previously considered protective against fractures. Additionally, rather than the spine, the fracture occurred in the hip, which is an uncommon site for mastocytosis-induced fractures. Conclusion: Mastocytosis is a rare cause of osteoporosis, and it is important to keep this condition in the differential diagnosis of osteoporosis, particularly when the fracture presentation is atypical.

Free mebrofenin clearance.

OBJECTIVES: To determine if three new simplified equations for measurement of free mebrofenin clearance give similar results to the equations defined by Ekman et. al ., and to evaluate the properties of all four methods. Regional mebrofenin clearance has been used to predict future remnant liver function and liver failure after regional liver therapy, such as partial hepatic resection. METHODS: The means, standard deviations, and correlations of the free mebrofenin clearance measured by the Ekman method and the three simplified methods were compared in a consecutive series of 26 studies in 20 patients. The fractional change in the blood and free mebrofenin activities were compared, and integrals of normalized blood and free mebrofenin ("effective times") were compared. RESULTS: The average percent free mebrofenin clearance for the Ekman and the first, second and third simplified methods were 13.62 ± 2.88%/min, 12.98 ± 2.97%/min, 12.52 ± 2.81%/min and 15.03 ± 2.27%/min, respectively. The correlations of the new methods with Ekman were 0.97, 0.93 and 0.93. The fractional changes during the measurement interval for the blood and free mebrofenin activities were 0.381 ± 0.065 and 0.329 ± 0.062, difference 0.052, P < 0.5. The integrals of normalized blood and free mebrofenin activities were 2.566 ± 0.160 min and 2.661 ± 0.158 min, difference of 0.094 min and P < 0.05. CONCLUSIONS: The results of the three new methods were similar to the Ekman method. The first simplified method was identified as the lead method for clinical validation in a larger population.

Tumor-induced osteomalacia treated with T12 tumor resection.

Summary: Tumor-induced osteomalacia (TIO) is a rare form of osteomalacia caused by fibroblast growth factor-23 (FGF23)-secreting tumors. Most of these tumors are phosphaturic mesenchymal tumors (PMTs) typically involving soft tissue in the extremities and bone of the appendicular skeleton and cranium. We report the case of a 60-year-old woman with about 3 years of persistent bone pain and multiple fractures, initially diagnosed as osteoporosis, who was found to have hypophosphatemia with low 1,25-dihydroxyvitamin D and elevated alkaline phosphatase and inappropriately normal FGF23 consistent with TIO. Her symptoms improved with phosphate supplementation, vitamin D and calcitriol. 68Ga-DOTATATE imaging revealed a T12 vertebral body lesion confirmed on biopsy to be a PMT. She underwent resection of the PMT with resolution of TIO and increased bone density. This rare case of TIO secondary to a PMT of the thoracic spine highlights some of the common features of PMT-associated TIO and draws attention to PMT-associated TIO as a possible cause of unexplained persistent bone pain, a disease entity that often goes undiagnosed and untreated for years. Learning points: Tumor-induced osteomalacia (TIO) is typically caused by phosphaturic mesenchymal tumors (PMTs) that are usually found in the soft tissue of the extremities and bone of the appendicular skeleton/cranium and rarely in the spine. TIO may be misdiagnosed as osteoporosis or spondyloarthritis, and the correct diagnosis is often delayed for years. However, osteoporosis, in the absence of fracture, is not associated with bone pain. The hallmark of TIO is hypophosphatemia with inappropriately normal or low 1,25-dihydroxyvitamin D and elevated or inappropriately normal fibroblast growth factor-23 (FGF23) levels. In patients with unexplained persistent bone pain, a serum phosphate should be measured. Consider PMT-associated TIO as a potential cause of unexplained persistent bone pain and hypophosphatemia. PMTs express somatostatin receptors and may be identified with 68Ga-DOTATATE imaging. Complete surgical resection is the preferred treatment for spinal PMTs associated with TIO.

Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation.

UNLABELLED: PET/CT imaging with (18)F-FDG has been used to detect inflammation in carotid and aortic plaque; its use in detecting coronary plaque has been limited by avid (18)F-FDG uptake by the myocardium. We investigated whether (18)F-FDG PET/CT could be used to image inflammation in coronary arteries as a potential noninvasive method to detect vulnerable plaque. METHODS: We retrospectively studied 32 patients treated for malignancy who underwent (18)F-FDG PET/CT and concomitant cardiac catheterization. As part of the recently described protocol, all patients were instructed to eat a low-carbohydrate, high-fat meal the night before and drink a vegetable oil drink the morning of the study. We reviewed the patients' baseline characteristics and their (18)F-FDG PET/CT scans for adequacy of myocardial uptake suppression and correlated the presence of angiographically apparent plaque with (18)F-FDG uptake in the major coronary arteries. Two independent observers assessed the angiographic images and (18)F-FDG PET scans. RESULTS: A total of 95% of patients had 2 or more coronary disease risk factors, and 25% had unstable symptoms; 30% of index catheterizations resulted in intervention. In 20 of 32 patients (63%), myocardial suppression was good (12) or adequate (8). Inadequate suppression was due to self-reported dietary nonadherence. Patients with good, adequate, and poor suppression had maximal myocardial standardized uptake values of 2.8 +/- 0.7, 5.0 +/- 1.3, and 17.0 +/- 9.7, respectively. We identified (18)F-FDG uptake in 15 patients in 1 or more coronary segments. A trend to significance in correlation between presence of angiographic disease and signal in the vessel was observed (P = 0.07; 80 vessels examined). A total of 7 patients with significant coronary artery disease had aortic (18)F-FDG uptake. CONCLUSION: In this retrospective study, we demonstrated the potential use of (18)F-FDG PET in imaging of inflammation in coronary arteries. The potential of (18)F-FDG PET is also being investigated in a prospective study.

Respiratory gating enhances imaging of pulmonary nodules and measurement of tracer uptake in FDG PET/CT.

OBJECTIVE: The aim of this study was to evaluate prospectively the effects of respiratory gating during FDG PET/CT on the determination of lesion size and the measurement of tracer uptake in patients with pulmonary nodules in a clinical setting. SUBJECTS AND METHODS: Eighteen patients with known pulmonary nodules (nine women, nine men; mean age, 61.4 years) underwent conventional FDG PET/CT and respiratory-gated PET acquisitions during their scheduled staging examinations. Maximum, minimum, and average standardized uptake values (SUVs) and lesion size and volume were determined with and without respiratory gating. The results were then compared using the two-tailed Student's t test and the nonparametric Wilcoxon's test to assess the effects of respiratory gating on PET acquisitions. RESULTS: Respiratory gating reduced the measured area of lung lesions by 15.5%, the axial dimension by 10.3%, and the volume by 44.5% (p = 0.014, p = 0.007, and p = 0.025, respectively). The lesion volumes in gated studies were closer to those assessed by standard CT (difference decreased by 126.6%, p = 0.025). Respiratory gating increased the measured maximum SUV by 22.4% and average SUV by 13.3% (p < 0.001 and p = 0.002). CONCLUSION: Our findings suggest that the use of PET respiratory gating in PET/CT results in lesion volumes closer to those assessed by CT and improved measurements of tracer uptake for lesions in the lungs.

Pitfalls of diagnosis based on abnormal flow cytometry and [(18)F]fluorodeoxyglucose positron emission tomography.

A 30-year-old, HIV-positive man with a previous history of an atypical nasopharyngeal Burkitt lymphoma developed fluorodeoxyglucose (FDG) avidity on a routine FDG-positron emission tomography (PET)/computed tomography scan performed 10 months after the completion of all treatment. This new FDG-avid disease was in the area of his initial disease. Flow cytometric assessment of a fine needle aspiration showed a CD10-expressing B-cell population with kappa predominance. The corresponding cytology smears had large atypical lymphoid cells along with smaller lymphocytes and macrophages. Because of the patient's previous history of a CD10(+), high-grade B-cell lymphoma, the cytologic and flow cytometric findings were considered highly suspicious for a B-cell lymphoma. Because the differential diagnosis included a relapsed Burkitt lymphoma versus a second, unrelated lymphoma (the former with a dismal prognosis) it was deemed prudent to obtain more tissue via an open biopsy for confirmation of diagnosis and exact subclassification. An open biopsy, however, revealed a reactive lymph node with enlarged geographic follicles; no lymphoma was demonstrable and c-Myc studies were negative. The patient remains without evidence of disease. Retrospectively, the original flow cytometric assessment was believed to likely represent sampling of hyperplastic germinal centers with significantly expanded CD10(+) B cells. The FDG uptake and the kappa predominance further confounded the interpretation. This case illustrates the pitfalls of standard diagnostic techniques, including PET scanning, cytology, and flow cytometry, particularly in the setting of HIV. It further underscores the importance of adequate clinical correlation and a low threshold for performing open biopsies in such patients.

Shareware program for nuclear medicine and PET/CT PACS display and processing.

OBJECTIVE: Many of the functions necessary for imaging and analyzing nuclear medicine studies are not available on radiology PACS. Over the past 20 years, we have developed a user-friendly, easily installed software package for nuclear medicine study analysis, display, Web access, and database storage and an integrated display for fused PET/CT. We are making this software available as free shareware that can be used without a license on any PC. The software package was developed as a cooperative effort between house and attending staff and our nuclear medicine programmer. Particular emphasis was put on making functions intuitive and user friendly. CONCLUSION: A shareware nuclear medicine PACS software package including a display for fused PET/CT studies has been developed, extensively clinically tested, and is freely available on the Internet.

Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping.

The use of near-infrared or infrared photons is a promising approach for biomedical imaging in living tissue. This technology often requires exogenous contrast agents with combinations of hydrodynamic diameter, absorption, quantum yield and stability that are not possible with conventional organic fluorophores. Here we show that the fluorescence emission of type II quantum dots can be tuned into the near infrared while preserving absorption cross-section, and that a polydentate phosphine coating renders them soluble, disperse and stable in serum. We then demonstrate that these quantum dots allow a major cancer surgery, sentinel lymph node mapping, to be performed in large animals under complete image guidance. Injection of only 400 pmol of near-infrared quantum dots permits sentinel lymph nodes 1 cm deep to be imaged easily in real time using excitation fluence rates of only 5 mW/cm(2). Taken together, the chemical, optical and in vivo data presented in this study demonstrate the potential of near-infrared quantum dots for biomedical imaging.

Extravazation of therapeutic yttrium-90-ibritumomab tiuxetan (zevalin): a case report.

The occurrence of radiation necrosis to the extravasation of therapeutic radionuclide-yttrium-90-ibritumomab tiuxetan-is described, as well as the subsequent steps taken to both address the occurrence and to prevent the re-occurrence of such an adverse event. Published reports on the extravasation of diagnostic and therapeutic radionuclides are reviewed, as are prevention and treatment protocols.

False-positive axillary lymph node on FDG-PET/CT scan resulting from immunization.

An initial CT of a 59-year-old man with increasing back pain and weight loss showed lymphadenopathy in multiple nodal beds. A biopsy showed diffuse, large B-cell lymphoma (DLBCL). After initial chemotherapy, residual disease prompted an autologous stem cell transplant. After a follow-up FDG-PET/CT scan showed no FDG-avid disease, a subsequent study showed FDG uptake in a nonenlarged left axillary lymph node. Questioning elicited a recent immunization history. A follow-up PET/CT scan showed no uptake in this lymph node and no disease recurrence. Without this history, an unnecessary biopsy or treatment may have ensued. Methods to avoid such occurrences are discussed.

Prone SPECT myocardial perfusion imaging is associated with less cardiac drift during the acquisition duration than imaging in the supine position.

BACKGROUND AND AIM: Cardiac cranial drift, a slow vertical upward displacement seen during the acquisition of myocardial single photon emission tomography (SPECT), is a source of image artefacts that may lead to erroneous interpretation. Changes in breathing pattern and depth throughout image acquisition are believed to cause cardiac cranial drift. As the physiology of respiration probably differs with postural changes, we hypothesized that cardiac drift may be different for supine vs. prone acquisitions. Our aim was to assess the magnitude of cardiac displacement for prone and supine SPECT acquisitions in patients undergoing stress myocardial perfusion imaging. METHODS: We enrolled prospectively 15 subjects undergoing exercise myocardial perfusion imaging. Subjects had post-stress images acquired in both the prone and supine positions. Motion was assessed in the horizontal (x) and vertical (y) axes for both camera heads at all 64 projections at which images were obtained. Pixel displacement (number of pixels from the baseline of zero) in either the cranial/caudal or left/right direction was quantified using the automated camera motion correction algorithm. RESULTS: Supine imaging was associated with more cranial drift than prone imaging (1.20+/-0.40 pixels vs. 0.92+/-0.24 pixels, P<0.05). There was no significant difference in cardiac displacement in the horizontal axis (1.03+/-0.5 pixels vs. 1.12+/-0.22 pixels, P=NS). CONCLUSIONS: Prone imaging is associated with less cardiac cranial drift than imaging in the supine position, suggesting that the former is associated with a more constant and reliable diaphragmatic breathing pattern. Acquisitions in the prone position may thus be associated with fewer motion artefacts than supine acquisitions for cardiac SPECT imaging.

Systems for remote interpretation of emergency studies.

Telenuclear medicine facilitates a timely expert interpretation of emergency nuclear medicine studies. Current, high-speed Internet connection allows nuclear medicine physicians to be on-call from their homes. Software to support telenuclear medicine is becoming more widely available, although the design of some departments makes implementation difficult. Quality control of the remote monitor requires special attention to ensure correct interpretation. Fortunately, monitor quality control can be performed quickly using relatively simple procedures. Thus, expert interpretation of emergency nuclear medicine studies is practical.

Sub-millimeter technetium-99m calibration sources.

PURPOSE: Small animal radioscintigraphic imaging systems aim to achieve sub-millimeter resolution. At the present time, sub-millimeter calibration sources that can be placed at will within an imaged volume are not readily available. We have developed a method for producing technetium-99m (Tc-99m) sources in less than 15 minutes with readily available reagents. PROCEDURES: Tc-99m pertechnetate [TcO(4)](-) was incubated with 45 microm to 106 microm diameter spherical anion exchange beads, washed, and mounted as desired for instrument calibration. RESULTS: The procedure yields spherical sources having between 6.8 microCi to 11.1 microCi of Tc-99m per source. This work shows that dual imaging of these sources using white light and radioscintigraphy permits measurement of system performance with high precision. CONCLUSION: Easily prepared, sub-millimeter Tc-99m spherical calibration sources are described, and it is demonstrated that such sources are useful for measuring the resolution and sensitivity of radioscintigraphic systems, such as those designed for small animal imaging.

ECG-gated 99mTc single-photon emission CT for assessment of right ventricular structure and function: is the information provided similar to echocardiography?

STUDY OBJECTIVE: (99m)Tc single-photon emission CT (SPECT) and ECG-gated SPECT can visualize well the right ventricle (RV) in most patients, but their utility for assessment of the RV has not been formally evaluated. We examined whether (99m)Tc SPECT/ECG-gated SPECT provide similar information to transthoracic two-dimensional Doppler echocardiography (2D-ECHO) regarding RV cavity size, wall thickness, and systolic function. DESIGN: Retrospective analysis. SETTING: A major university teaching hospital. PATIENTS: A consecutive series of 194 patients with good quality stress SPECT and 2D-ECHO studies performed within 1 day of each other and no significant interim cardiac events. MEASUREMENTS AND RESULTS: RV size and function were visually assessed by SPECT/ECG-gated SPECT and 2D-ECHO. RV wall thickness was visually assessed by SPECT and measured in mm in end-diastole by 2D-ECHO. Of 142 patients with normal RV cavity size by SPECT, 134 patients (94%) had normal RV cavity size by 2D-ECHO. However, of 52 patients with RV dilation by SPECT, only 9 patients (17%) had RV dilation by 2D-ECHO. A perfusion abnormality in the right coronary artery territory was significantly associated with RV dilation by SPECT (p < 0.005) and 2D-ECHO (p < 0.05). Among 150 patients with ECG-gated SPECT, only 2 patients had abnormal RV systolic function, as compared with 18 patients by 2D-ECHO. RV wall thickness measurements by SPECT and 2D-ECHO did not correlate. CONCLUSIONS: For normal interpretations regarding RV cavity size, wall thickness, and systolic function, there is good agreement between (99m)Tc stress SPECT/ECG-gated SPECT and 2D-ECHO. However, there is poor overall agreement between gated SPECT/ECG-gated SPECT and 2D-ECHO regarding the presence of RV dilation, hypertrophy, and systolic dysfunction.

Long-term effects of surgical angiogenic therapy with fibroblast growth factor 2 protein.

OBJECTIVE: The long-term effects of surgical fibroblast growth factor 2 therapy are examined. METHODS: In a randomized, double-blind study, fibroblast growth factor 2 (10 microg or 100 microg) or placebo (n = 8 each) was delivered in the ungraftable myocardial territory of patients concomitantly undergoing coronary artery bypass grafting. Patients were followed up to 32.2 +/- 6.8 months postoperatively with clinical assessment and nuclear perfusion imaging. RESULTS: Baseline patient characteristics were similar between the 3 groups. There were 2 late deaths, one of pancreatic cancer and one of undetermined cause (both in the 100-microg fibroblast growth factor 2 group). Two patients (both in the control group) underwent a total of 6 repeat cardiac catheterizations for recurrent coronary events. Mean Canadian Cardiovascular Society angina class improved at late follow-up from baseline in all groups (P < or = .02); however, patients treated with either dose of fibroblast growth factor 2 had significantly more freedom from angina recurrence than those treated with placebo (P =.03). Late nuclear perfusion scans revealed a persistent reversible or a new, fixed perfusion defect in the ungraftable territory of 4 of 5 patients who received placebo versus only 1 of 9 patients treated with fibroblast growth factor 2 (P =.02). The overall sum of left ventricular stress perfusion defect scores was also lower in fibroblast growth factor 2-treated patients than in control subjects (1.3 +/- 1.4 vs 3.9 +/- 2.1, respectively; P =.04). A trend toward a higher late left ventricular ejection fraction was noted in fibroblast growth factor 2-treated patients (55.1% +/- 14.6% vs 44.3% +/- 6.5%, fibroblast growth factor 2-treated patients versus control subjects; P =.12). CONCLUSIONS: These data suggest that surgical angiogenic therapy with sustained-release fibroblast growth factor 2 may result in a prolonged myocardial revascularization effect that could translate into clinical benefit.

Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients.

The aims of this study were to: (1) assess the effects of repetitive transcranial magnetic stimulation (rTMS) on brain activity in depressed patients as measured by single photon emission tomography (SPECT); (2) evaluate the predictive value of brain SPECT on the antidepressant efficacy of rTMS. Patients (n=17) received 1600 rTMS stimuli at a rate of 10 Hz, 5 days per week for 2 weeks to the left dorsolateral prefrontal cortex. Whole brain SPECT data were acquired using Tc99m-Bicisate. Regional cerebral blood flow (rCBF) was correlated with the % change in the 28-item Hamilton Depression Rating Scale Score (Delta-HDRS) and a semiquantitative region of interest (ROI) analysis was conducted. Prior to rTMS there was a significant left-right asymmetry favoring the right, whereas 2 weeks after the rTMS treatment this asymmetry was reversed. The rCBF in limbic structures was negatively correlated with the outcome and rCBF in several neocortical areas was positively correlated. Brain SPECT can provide information about mechanisms of action of rTMS and may have predictive value for the antidepressant efficacy of rTMS.

ACR Appropriateness Criteria non-invasive clinical staging of bronchogenic carcinoma.

In order to appropriately manage patients with lung cancer, it is necessary to properly stage the tumor. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.