Donald R. Neumann

Usefulness of 123I-MIBG Scintigraphy in the Evaluation of Patients with Known or Suspected Primary or Metastatic Pheochromocytoma or Paraganglioma: Results from a Prospective Multicenter Trial

Although 123I-MIBG has been in clinical use for the imaging of pheochromocytoma for many years, a large multicenter evaluation of this agent has never been performed. The present study was designed to provide a prospective confirmation of the performance of 123I-MIBG scintigraphy for the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma. Methods: A total of 81 patients with a prior history of primary or metastatic pheochromocytoma or paraganglioma and 69 with suspected pheochromocytoma or paraganglioma based on symptoms of catecholamine excess, CT or MRI findings, or elevated catecholamine or metanephrine levels underwent whole-body planar and selected SPECT 24 h after the administration of 123I-MIBG. Images were independently interpreted by 3 masked readers, with consensus requiring agreement of at least 2 readers. Final diagnoses were based on histopathology, correlative imaging, catecholamine or metanephrine measurements, and clinical follow-up. Results: Among 140 patients with definitive diagnoses (91, disease present; 49, disease absent), 123I-MIBG planar scintigraphy had a sensitivity and specificity of 82%. For patients evaluated for suspected disease, sensitivity and specificity were 88% and 84%, respectively. For the subpopulations of adrenal (pheochromocytoma) and extraadrenal (paraganglioma) tumors, sensitivities were 88% and 67%, respectively. The addition of SPECT increased reader confidence but minimally affected sensitivity and specificity. Conclusion: This prospective study demonstrated a sensitivity of 82%−88% and specificity of 82%−84% for 123I-MIBG imaging used in the diagnostic assessment of primary or metastatic pheochromocytoma or paraganglioma.

Preoperative 123I/99mTc-Sestamibi Subtraction SPECT and SPECT/CT in Primary Hyperparathyroidism

The trend toward focused surgical parathyroidectomy requires precise preoperative localization of parathyroid lesions in patients with hyperparathyroidism. The purpose of this study was to directly compare the diagnostic accuracy of 99mTc-sestamibi/123I subtraction SPECT with SPECT/CT for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism. Methods: A total of 61 consecutive surgical patients with primary hyperparathyroidism underwent both 123I/99mTc-sestamibi subtraction SPECT and SPECT/CT scans preoperatively, using a hybrid SPECT/CT instrument that combined a dual-detector SPECT camera with a 6-slice multidetector spiral CT scanner. Four hours after being given 123I-sodium iodide orally, each patient received 99mTc-sestamibi intravenously, followed immediately by a simultaneous, dual-isotope SPECT scan of the neck and upper chest. Then, without moving the patient, we performed a non–contrast-enhanced CT scan of the same body region. Normalization and subtraction of the 123I SPECT images from the 99mTc SPECT images were performed. The subtraction SPECT and the coregistered fused SPECT/CT studies were interpreted separately, with images scored on a 5-point scale. Surgical and histopathologic findings were used as the standard of comparison. Results: Surgery was successful in 57 patients (solitary parathyroid adenoma in 48 patients, double parathyroid adenomas in 6 patients, and 10 hyperplastic parathyroid glands in 3 patients). The sensitivities of SPECT (50/70 = 71%) and SPECT/CT (49/70 = 70%) were similar (P = 0.779). The specificity of SPECT/CT (26/27 = 96%) was significantly greater than that of SPECT (13/27 = 48%; P = 0.006). The receiver-operating-characteristic area under the curve of SPECT/CT (0.833) was significantly greater than that of SPECT (0.632; P < 0.001). Conclusion: SPECT/CT is significantly more specific than dual-isotope subtraction SPECT for the preoperative identification of parathyroid lesions in patients with primary hyperparathyroidism.

Fasting 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography to Detect Metabolic Changes in Pulmonary Arterial Hypertension Hearts over 1 Year

BACKGROUND The development of tools to monitor the right ventricle in pulmonary arterial hypertension (PAH) is of clinical importance. PAH is associated with pathologic expression of the transcription factor hypoxia-inducible factor (HIF)-1α, which induces glycolytic metabolism and mobilization of proangiogenic progenitor (CD34(+)CD133(+)) cells. We hypothesized that PAH cardiac myocytes have a HIF-related switch to glycolytic metabolism that can be detected with fasting 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography (FDG-PET) and that glucose uptake is informative for cardiac function. METHODS Six healthy control subjects and 14 patients with PAH underwent fasting FDG-PET and echocardiogram. Blood CD34(+)CD133(+) cells and erythropoietin were measured as indicators of HIF activation. Twelve subjects in the PAH cohort underwent repeat studies 1 year later to determine if changes in FDG uptake were related to changes in echocardiographic parameters or to measures of HIF activation. MEASUREMENTS AND RESULTS FDG uptake in the right ventricle was higher in patients with PAH than in healthy control subjects and correlated with echocardiographic measures of cardiac dysfunction and circulating CD34(+)CD133(+) cells but not erythropoietin. Among patients with PAH, FDG uptake was lower in those receiving β-adrenergic receptor blockers. Changes in FDG uptake over time were related to changes in echocardiographic parameters and CD34(+)CD133(+) cell numbers. Immunohistochemistry of explanted PAH hearts of patients undergoing transplantation revealed that HIF-1α was present in myocyte nuclei but was weakly detectable in control hearts. CONCLUSIONS PAH hearts have pathologic glycolytic metabolism that is quantitatively related to cardiac dysfunction over time, suggesting that metabolic imaging may be useful in therapeutic monitoring of patients.

SPECT/CT Imaging : Clinical Utility of an Emerging Technology

Single-photon emission computed tomography (SPECT) has been a mainstay of nuclear medicine practice for several decades. More recently, combining the functional imaging available with SPECT and the anatomic imaging of computed tomography (CT) has gained more acceptance and proved useful in many clinical situations. Most vendors now offer integrated SPECT/CT systems that can perform both functions on one gantry and provide fused functional and anatomic data in a single imaging session. In addition to allowing anatomic localization of nuclear imaging findings, SPECT/CT also enables accurate and rapid attenuation correction of SPECT studies. These attributes have proved useful in many cardiac, general nuclear medicine, oncologic, and neurologic applications in which the SPECT results alone were inconclusive. Optimal clinical use of this rapidly emerging imaging modality requires an understanding of the fundamental principles of SPECT/CT, including quality control issues as well as potential pitfalls and limitations. The long-term clinical and economic effects of this technology have yet to be established.

Evaluation of preoperative ProstaScint scans in the prediction of nodal disease.

Diagnostic methods are limited for detecting microscopic soft tissue metastases in patients with prostate cancer. Previous studies using 111Indium Capromab Pendetide (ProstaScint™ scan) analyzed patients with extensive localized tumor (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We evaluated the role of the ProstaScint™ scan in a preoperative population to provide histological documentation and to assess its utility in a surgical population. A total of 22 preoperative patients, underwent a ProstaScint™ scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9–33 ng/ml). The mean Gleason score at biopsy was 6.9 (range 6–9). Each patient underwent a radical retropubic prostatectomy and bilateral pelvic lymph node dissection, which included resection of both obturator and common iliac lymph nodes. Histologic analysis of the resected lymph nodes provided the standard of comparison with the ProstaScint™ scan. The results of the scan and pathology for all 22 patients were compared with the bilateral obturator and iliac nodes, creating 88 data points. Nine areas (10%) were positive on the scan. One of these (11%) was a true positive while the other eight (89%) were false positives. Seventy-nine areas (90%) were negative on scan results. Of these, five areas (6%) were false negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 11%. The high false positive rate and low PPV of ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful when used preoperatively.

The incidence of scintigraphically viable and nonviable tissue by rubidium-82 and fluorine-18-fluorodeoxyglucose positron emission tomographic imaging in patients with prior infarction and left ventricular dysfunction

BackgroundAlthough reversible perfusion defects, perfusion-metabolism mismatch and match patterns are important for differentiating viable from nonviable myocardium, the frequency of these scintigraphic patterns has not been reported. The study objective was to establish the incidence of these scintigraphic patterns to estimate the clinical need for metabolic positron emission tomography for evaluating tissue viability in patients with prior myocardial infarction (MI).Methods and Results82Rb perfusion images were interpreted to identify reversible or irreversible defects, followed by determination of their 18F-fluorodeoxyglucose (18F-FDG) uptake pattern. In 155 patients with prior MI, analysis of 613 abnormal segments showed reversible perfusion defects in 13%. The 87% irreversible defects, 18% showed perfusion-metabolism mismatch, whereas 69% showed the match pattern. Reversible perfusion defects and perfusion-metabolism mismatches were noted in 20% (31/155) and 29% (45/155) of patients, respectively, whereas the match pattern was noted in 51% (79/155) of patients.ConclusionIrreversible perfusion defects were common in our patients with prior MI, and distinction between viable and nonviable tissue was not possible by perfusion imaging alone. The identification of hibernating myocardium was possible only with the additional 18F-FDG imaging in about one third of patients. This indicates a significant clinical demand for 18F-FDG imaging that identifies patients who will benefit from revascularization.

Robotic thoracoscopic mediastinal parathyroidectomy for persistent hyperparathyroidism: case report and review of the literature.

Recurrent and persistent primary hyperparathyroidism remains a significant surgical challenge. Abnormal, hypersecreting parathyroid glands are found in ectopic locations in up to 15% to 20% of patients. A small portion of these ectopic glands will be found in the mediastinum at a location that precludes removal through the traditional cervical incision. Minimally invasive approaches to these glands are desirable because of the significant morbidity, pain, and hospital stay associated with sternotomy or thoracotomy. Recently, robotic approaches have been described for mediastinal parathyroids. We report a case of young woman with persistent primary hyperparathyroidism who was cured after undergoing robotic thoracoscopic mediastinal parathyroidectomy using radiooperative and intraoperative parathyroid hormone guidance.

Regional body FDG-PET in postoperative recurrent hyperparathyroidism

PURPOSE The use of preoperative imaging studies in patients with persistent or recurrent hyperparathyroidism after initial operation is generally accepted to improve the success rate and minimize the morbidity from reoperative surgery. The purpose of this study was to define the performance of FDG-PET for the localization of hyperfunctioning parathyroid tissue prior to reoperation. METHOD Twenty patients with biochemical evidence of recurrent or persistent hyperparathyroidism following previous neck surgery were investigated. Regional body PET imaging of the neck and upper chest (axial field of view 27.5 cm) was acquired 45 min after 5-10 mCi FDG was given intravenously. RESULTS Subsequent surgery revealed solitary parathyroid adenomas in 14 patients, seven hyperplastic glands in 2 patients, and parathyroid carcinoma in 1 patients. FDG-PET correctly identified 79% (11/14) of the parathyroid adenomas, 29% (2/7) of the hyperplastic glands, and the parathyroid carcinoma. FDG-PET was negative in 79% (30/38) of the surgically identified normal parathyroid glands. Eight false-positive findings led to a positive predictive value of 64%. CONCLUSION These preliminary data suggest that regional body FDG-PET is a promising procedure in the evaluation of patients with persistent or recurrent postoperative hyperparathyroidism.

Preliminary experience with double-phase SPECT using Tc-99m sestamibi in patients with hyperparathyroidism

BACKGROUND There is a continual search for a better imaging modality for parathyroid pathology. In recent years, Tc-99m sestamibi has been proposed as an alternative to T1-201 for parathyroid scintigraphy. The purpose of this study is to assess the usefulness of a double-phase Tc-99m sestamibi SPECT technique for parathyroid imaging. METHODS Sixty-one consecutive patients with hyperparathyroidism were studied. Sixteen had previously undergone unsuccessful surgery for hyperparathyroidism. SPECT imaging of the neck and chest was performed at 15 minutes and again at 2 hours after 20-25 mCi of Tc-99m sestamibi was given intravenously. A positive scan was defined as a region of increased focal uptake that persisted on the delayed images. RESULTS When compared with surgical findings, double-phase sestamibi SPECT correctly identified 55% (26/ 47) of the parathyroid adenomas in the previously unoperated group, and 91% (10/11) of the parathyroid adenomas in the reoperative group. Double-phase sestamibi SPECT was negative in 92% (109/118) of the normal parathyroid glands in the previously unoperated group, and in 88% (15/17) in the reoperative group. CONCLUSIONS These preliminary data suggest that double-phase Tc-99m sestamibi SPECT is a promising procedure for the preoperative detection and localization of hyperfunctioning parathyroid tissue, especially in patients with recurrent or persistent postoperative hyperparathyroidism.

The impact of functional imaging on radiation medicine

Radiation medicine has previously utilized planning methods based primarily on anatomic and volumetric imaging technologies such as CT (Computerized Tomography), ultrasound, and MRI (Magnetic Resonance Imaging). In recent years, it has become apparent that a new dimension of non-invasive imaging studies may hold great promise for expanding the utility and effectiveness of the treatment planning process. Functional imaging such as PET (Positron Emission Tomography) studies and other nuclear medicine based assays are beginning to occupy a larger place in the oncology imaging world. Unlike the previously mentioned anatomic imaging methodologies, functional imaging allows differentiation between metabolically dead and dying cells and those which are actively metabolizing. The ability of functional imaging to reproducibly select viable and active cell populations in a non-invasive manner is now undergoing validation for many types of tumor cells. Many histologic subtypes appear amenable to this approach, with impressive sensitivity and selectivity reported.For clinical radiation medicine, the ability to differentiate between different levels and types of metabolic activity allows the possibility of risk based focal treatments in which the radiation doses and fields are more tightly connected to the perceived risk of recurrence or progression at each location.This review will summarize many of the basic principles involved in the field of functional PET imaging for radiation oncology planning and describe some of the major relevant published data behind this expanding trend.