Biomedical subjects

Michael K O'Connor

Publications and source records attributed to Michael K O'Connor.

18 recordsLinked to original sources

PubMed2006

Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter.

PURPOSE: MV-CEA is an oncolytic measles virus currently being tested in patients with ovarian cancer and whose propagation can be monitored by measuring blood carcinoembryonic antigen (CEA) levels. MV-NIS is an oncolytic measles virus coding for the thyroidal sodium iodide symporter (NIS) whose propagation can be mapped by serial radioiodine imaging. Expression of both CEA and NIS genes from a single virus would combine sensitive, quantitative expression monitoring (CEA) with radioisotopic expression mapping (NIS). Because of the unfavorable replication kinetics of measles viruses expressing both CEA and NIS, we explored the feasibility of combining MV-CEA with MV-NIS for comprehensive virotherapy monitoring in ovarian cancer. EXPERIMENTAL DESIGN AND RESULTS: Mice implanted with i.p. SKOV3ip.1 ovarian cancer xenografts received MV-CEA alone, MV-NIS alone, or a combination of MV-CEA plus MV-NIS. Viral gene expression was monitored by measuring blood CEA levels, and the location of virus-infected cells was monitored by gamma camera imaging. Surprisingly, mice receiving the combination of MV-CEA plus MV-NIS showed greatly superior responses to therapy, but this was associated with 10-fold lower plasma levels of CEA compared with mice treated with MV-CEA alone. In vitro studies showed superior replication kinetics of MV-NIS relative to MV-CEA. The gamma camera scans were considerably less sensitive than the plasma CEA marker for monitoring virus infection. CONCLUSIONS: Dual therapy with MV-CEA and MV-NIS is superior to treatment with either virus alone, and it allows noninvasive monitoring of virotherapy via soluble marker peptide and gamma camera imaging. This has important implications for the clinical development of oncolytic measles viruses.

Animals↗

PubMed2006

Differences in left ventricular ejection fraction and volumes measured at rest and poststress by gated sestamibi SPECT.

BACKGROUND: Some studies suggested that the poststress left ventricle ejection fraction (LV EF) is lower than rest LV EF in patients with stress-induced ischemia. METHODS AND RESULTS: By using a 2-day protocol and 30 mCi Tc-99m sestamibi, LV EF, end-systolic volume (ESV), and end-diastolic volume (EDV) were measured with gated SPECT. Of 99 eligible patients, 91 had technically adequate studies. Poststress LV EF minus rest LV EF was defined as DeltaLV EF. DeltaEDV and DeltaESV were similarly defined. Rest and poststress LV EF (r = 0.89), EDV (r = 0.78), and ESV (r = 0.93) were highly correlated (P <.001). Rest LV EF, EDV, and ESV were not significantly different between patients with and without stress-induced ischemia. DeltaLV EF was significantly lower in patients with stress-induced ischemia (-3.5% +/- 4.5% vs -1.1% +/- 4.7%, P = .02). Mean LV EF poststress in ischemic patients was 55.0% +/- 10.5% vs 61.2% +/- 10.0% in nonischemic patients (P = .008). However, only 1 patient (3%) with ischemia had DeltaLV EF that exceeded the 95% confidence limit of DeltaLV EF for normal patients. Ischemia was significantly associated with increased DeltaEDV and DeltaESV (P < .01). CONCLUSIONS: Stress-induced ischemia is associated with poststress reduction in LV EF and increased poststress EDV and ESV. However, the effect of ischemia on the difference between poststress and rest EF measurements is modest and rarely exceeds the confidence limits in normal patients undergoing 2-day protocols. In most patients, poststress LV EF is an accurate reflection of rest LV EF.

Aged↗

PubMed2006

Single-photon emission computed tomography/computed tomography: basic instrumentation and innovations.

Correlation of the anatomical and functional information presented by single-photon emission computed tomography (SPECT) and computed tomography (CT) can aid in the decision-making process by enabling better localization and definition of organs and lesions and improving the precision of surgical biopsies. Technical developments over the past 20 years have led to the development of better software techniques for image fusion and, more recently, to the development of modern SPECT/CT systems. While image fusion techniques have been in clinical use for many years, the first commercial SPECT/CT system was only developed in 1999. Following the commercial success of PET/CT systems that employed multidetector CT (MDCT) scanners, there has been renewed interest in the development of comparable SPECT/CT systems. This has resulted in the development of a range of SPECT/CT devices varying from a simple CT add-on to a conventional SPECT system that can provide low-dose CT images to a full MDCT scanner integrated with a SPECT system. The advantages of combining SPECT with CT are numerous and are primarily due to the anatomic referencing and the attenuation correction capabilities of CT. Depending on system design, there are varying technical issues surrounding the different SPECT/CT devices, ranging from cost, radiation dose, planning, and siting requirements to system-specific issues such as table sag and CT artifacts due to patient motion. Motion artifacts should be less prevalent with the faster acquisition times of modern scanners, but are still problematic in the thorax and have not yet been fully resolved as they pertain to the use of CT data for cardiac attenuation correction. As this technology matures, we can expect to see a range of SPECT/CT devices available on the market that range from low-dose 1-4 slice inexpensive CT upgrades of conventional SPECT systems, to SPECT systems incorporating 64 or 128 slices CT scanners. The cost of the high-end CT scanners will exceed the cost of the SPECT scanner and hence the justification for such devices will be heavily dependent on clear demonstration of their value in clinical practice.

Equipment Design↗

PubMed2006

Adenovirus-mediated and targeted expression of the sodium-iodide symporter permits in vivo radioiodide imaging and therapy of pancreatic tumors.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. It is highly aggressive with no uniformly effective chemotherapy available for metastatic disease. The sodium-iodide symporter (NIS) is a transmembrane protein responsible for uptake of iodide into cells. The presence of NIS in thyroid cells permits diagnostic imaging and therapy of thyroid tumors, using radioiodide. Previous studies from this laboratory reported mucin-1 (MUC1)-driven expression of NIS in cancer cells. MUC1 overexpression has also been reported in 90% of pancreatic tumors. In this study Ad5/MUC1/NIS was used to infect pancreatic cancer cells both in vitro and in vivo, to investigate the potential for radioiodide imaging and ablation of this disease. In vitro studies revealed a 43-fold increase in iodide uptake in NIS-transduced cells compared with controls. In vivo imaging revealed effective iodide uptake and retention at the site of NIS-transduced tumors, with optimal uptake (13% of injected dose) observed 5 hr after iodide administration. Intravenous delivery was performed to investigate potential hepatotoxicity of the construct in the event of virus leakage. Intravenous injection of Ad5/CMV/NIS resulted in robust iodide uptake throughout mouse liver, whereas no uptake was detected in the liver of animals given Ad5/MUC1/NIS intravenously. Administration of therapeutic doses of 131I resulted in significant regression of NIS-transduced tumors, with a mean 50% reduction in volume within 10 weeks of therapy (p<0.0001). The ability to target NIS expression to pancreatic cancer, which has such limited treatment options, may be highly beneficial and warrants further investigation.

Adenoviridae↗

PubMed2005

A preclinical large animal model of adenovirus-mediated expression of the sodium-iodide symporter for radioiodide imaging and therapy of locally recurrent prostate cancer.

The sodium-iodide symporter (NIS) is primarily a thyroid protein, providing for the accumulation of iodide for biosynthesis of thyroid hormones. Native NIS expression has made possible the use of radioactive iodide to image and treat thyroid disease successfully. The current study, using adult male beagle dogs, was carried out in preparation for a Phase I clinical trial of adenovirus-mediated NIS gene (approved symbol SLC5A5) therapy for prostate cancer. Direct intraprostatic injection of virus (Ad5/CMV/NS) was followed by iv injection of 3 mCi 123I and serial image acquisition. The dogs were then given a therapeutic dose of 131I (116 mCi/m2) and observed for 7 days. SPECT/CT fusion imaging revealed clear images of the NIS-transduced prostates. Dosimetry calculations revealed an average absorbed dose to the prostate of 23 +/- 42 cGy/mCi 131I, with acceptably low radiation doses to other organs. This study demonstrated the successful introduction of localized NIS expression in the prostate gland of dogs, with no vector-related toxicity observed. None of the animals experienced any surgical complications, and serum chemistry panels showed no significant change following therapy. The results presented provide further evidence of the safety and efficacy of NIS as a therapeutic gene and support translation of this work into the clinical setting.

Adenoviridae↗

PubMed2005

Osteoporosis assessment by whole body region vs. site-specific DXA.

The ability of regional data from whole body scans to provide an accurate assessment of site-specific BMD, osteoporosis prevalence and fracture risk has not been fully explored. To address these issues, we measured total body (TBBD) and site-specific BMD in an age-stratified population sample of 351 women (21-93 years) and 348 men (22-90 years). We found an excellent correlation between AP lumbar spine and total body lumbar spine subregion BMD (r2=0.92), but weaker ones for total hip compared to pelvis region (r2=0.72) or between total wrist and left arm subregion from the whole body scan (r2=0.83). The error in estimating site-specific BMD from total body regions ranged from 4.3% (lumbar spine) to 11.2% (femoral neck) in women and from 4.9 to 11.1%, respectively, in men. Site-specific versus regional measurements at the lumbar spine and total hip/pelvis provided comparable overall estimates of osteoporosis prevalence, but disagreed on the status of individuals; measurements at whole body regions underestimated osteoporosis as assessed at the femoral neck or total wrist. All measurements were associated with a history of various fractures [age adjusted odds ratios (OR), 1.3 to 2.1 in women and 1.2 to 1.5 in men] and were generally interchangeable, but femoral neck BMD provided the best estimate of osteoporotic fracture risk in women (OR, 2.9; 95% CI, 1.7-5.0). Although there are strong correlations between BMD from dedicated scans of the hip, spine and distal forearm and corresponding regions on the whole body scan, the measurements provide somewhat different estimates of osteoporosis prevalence and fracture risk.

Absorptiometry, Photon↗

PubMed2005

Molecular breast imaging: a new technique using technetium Tc 99m scintimammography to detect small tumors of the breast.

OBJECTIVE: To determine the sensitivity of molecular breast imaging (MBI) to detect small cancers of the breast. PATIENTS AND METHODS: A cadmium-zinc-telluride gamma camera with a field of view of 20 x 20 cm was used. The detector elements were 2.5 x 2.5 mm. The gamma camera was mounted on a modified mammographic gantry. Between November 2001 and March 2004, we performed MBI on patients who were scheduled to undergo biopsy for a lesion suggestive of malignancy that was smaller than 2 cm on a mammogram. Patients were injected with 20 mCi of technetium Tc 99m sestamibi and underwent imaging immediately after injection. Using light pain-free compression, we obtained craniocaudal and mediolateral oblique views of each breast. RESULTS: Of the 40 women included in the study, 26 had a total of 36 malignant lesions confirmed at surgery. Of these 36 lesions, 33 were detected by MBI (overall sensitivity, 92%). Of the 22 malignant lesions 1 cm or smaller in diameter, 19 were detected by MBI (sensitivity, 86%). Two patients had false-negative MBI results. Of the 14 malignant lesions larger than 1 cm in diameter, all were identified correctly by MBI. In 4 patients, MBI identified additional lesions not seen on mammography that were confirmed subsequently on magnetic resonance imaging and were true-positive cases at surgery. Three of these patients had lesions in the breast contralateral to the breast containing the initial mammographic finding suggestive of malignancy. Of 14 patients with no evidence of cancer at biopsy or surgery, 9 had true-negative (normal) scans and 5 had false-positive scans on MBI. False-positive results included benign fibroadenoma (2 patients), inflammatory fat necrosis (1 patient), benign breast parenchyma (1 patient), and complex sclerosing lesion (1 patient). CONCLUSION: This prototype gamma camera system for MBI reliably detects malignant breast lesions smaller than 2 cm. Furthermore, we obtained the highest sensitivity (86%) yet reported for the detection of lesions smaller than 1 cm. These results suggest an important role for MBI, particularly for women in whom the sensitivity of mammography is reduced by the density of the breast parenchyma.

Adult↗

PubMed2005

Effect of tomographic orbit and type of rotation on apparent myocardial activity.

OBJECTIVES: In myocardial perfusion imaging, the type of orbit that provides the best image quality is still the subject of debate. This study correlates the effects of angular rotation (180 degrees vs. 360 degrees), type of orbit (circular vs. body contouring) and location of the heart within the orbit, with changes in spatial resolution and consequential changes in the uniformity of short axis slices of a normal myocardial phantom. METHODS: All studies were performed on a dual-head gamma camera equipped with low energy all-purpose collimators. A myocardium was suspended in air with no scattering or attenuating material present. SPECT acquisitions were performed using circular and body-contouring orbits of various radii and with the myocardium at the maximum off-axis position. RESULTS: The average uniformity of myocardial short axis slices was approximately 4% for 360 degrees circular orbits and for 180 degrees circular orbits where the myocardium was close to the centre of rotation. With body-contouring orbits, the average uniformity increased to 8% and 18% when the myocardium was located on the long and short axes of rotation, respectively. Changes in system resolution with a rotation of >3 mm increased non-uniformities in the myocardial images. CONCLUSIONS: Changes in resolution associated with the angular rotation, type of orbit and myocardial location affect the apparent distribution of activity in short axis slices of the heart. The most uniform images were obtained with a 360 degrees circular orbit. Results with a 180 degrees circular orbit and both 360 degrees and 180 degrees body-contouring orbits were highly dependent on the location of the myocardium.

Heart↗

PubMed2005

Comparison of small field of view gamma camera systems for scintimammography.

OBJECTIVE: To compare the performance characteristics of three compact gamma camera systems for scintimammography. METHODS: A multi-crystal NaI system (Dilon 6800), a multicrystal CsI system (Digirad 2020tc Imager) and a prototype cadmium zinc telluride (CZT) detector were evaluated using a breast phantom with simulated tumours of 1.8-9.8 mm in diameter and a tumour to background ratio of 5.6 : 1. A conventional Anger-based gamma camera was also evaluated for comparative purposes. RESULTS: The conventional gamma camera had the highest intrinsic sensitivity of the four systems and utilized the highest resolution collimator. However, the prototype CZT and the CsI systems yielded the best spatial resolution over the range 0-5 cm from the collimator face and better visualized small (5-7 mm) tumours. CONCLUSION: In addition to the advantage of close proximity to the breast, two of the three compact detectors offered superior performance to a conventional gamma camera for scintimammography.

Breast↗

PubMed2005

Relationship of gastric emptying and volume changes after a solid meal in humans.

Noninvasive imaging has been developed to measure gastric volumes. The relationship between gastric emptying and volume postprandially is unclear. The aims were to 1) develop a 3-dimensional (3D) single photon emission-computed tomography (SPECT) method to simultaneously measure gastric volume and emptying postprandially, 2) describe the course of gastric volume change during emptying of the meal, and 3) assess a 3D method measuring gastric emptying. In 30 healthy volunteers, we used (111)In-planar and (99m)Tc-SPECT imaging to estimate gastric emptying and volume after a radiolabeled meal. A customized analysis program of SPECT imaging assessed gastric emptying. A Bland-Altman plot assessed the performance of the new SPECT analysis compared with planar analysis. Gastric volume postprandially exceeds the fasting volume plus meal volume. The course of volume change and gastric emptying differ over time. Higher differences in volumes exist relative to fasting plus residual meal volumes at 15 min (median 763 vs. 568 ml, respectively, P < 0.001), 1 h (median 632 vs. 524 ml, P < 0.001), and 2 h (median 518 vs. 428 ml, P < 0.02), in contrast to similar volumes at 3 h (median 320 vs. 314 ml, P = 0.85). Analysis of SPECT imaging accurately measures gastric emptying compared with planar imaging with median differences of 1% (IQR -2.25 to 2.0) at 1 h, 1% (-3.25 to 2.25) at 2 h, and -2.5% (-4 to 0) at 3 h. Gastric volume exceeds meal volume during the first 2 postprandial hours, and simultaneous measurements of gastric volume and emptying can be achieved with a novel 3D SPECT method.

Adult↗

PubMed2005

Quantitation of regional ejection fractions using gated tomographic imaging with 99mTc-sestamibi.

BACKGROUND: Gated single photon emission CT (SPECT) sestamibi imaging allows the simultaneous assessment of myocardial perfusion and left ventricular function. OBJECTIVE: The purpose of this study was to evaluate a technique for quantitative regional wall motion assessment using gated SPECT (99m)Tc-sestamibi imaging. PATIENTS AND INTERVENTIONS: Fourteen subjects without cardiac pathology and 25 patients who had experienced myocardial infarction (MI) were studied. After tomographic reconstruction of gated short-axis slices, the identification of endocardial borders was made using a standard edge-detection program in systole and diastole in each of five selected slices. Regional ejection fraction (EF) and myocardial perfusion were determined for five regions within each slice. Ten patients underwent echocardiographic regional wall-motion analysis, the results of which were compared to corresponding regional EF results. RESULTS: High interobserver reproducibility in the assessment of regional EFs was found, with r values ranging from 0.94 to 0.98. In patients with anterior and inferior MIs, the regional EFs were abnormal in the anterior and septal regions, and the inferior and lateral regions, respectively. The regional EFs correlated significantly with regional perfusion in the anterior walls (r = 0.71; p = 0.0001), the lateral walls (r = 0.66; p = 0.0001), and inferior walls (r = 0.54; p = 0.0004). There was a significant association between the regional EFs and the echocardiographic regional wall motion assessment at the base (p < 0.0001), mid-ventricle (p = 0.0004), and apex (p = 0.0003). CONCLUSIONS: Gated SPECT images obtained (99m)Tc-sestamibi can provide reproducible quantitative, segmental regional EFs for multiple left ventricular slices that are significantly associated with subjective regional wall motion assessment by echocardiography.

Adult↗

PubMed2003

Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter.

The Edmonston vaccine strain of measles virus (MV-Edm) propagates efficiently in a broad range of human tumor cells, killing them selectively. However, the oncolytic potency of MV-Edm in different human tumor xenograft therapy models is highly variable and there is no convenient way to map the distribution of virus-infected tissues in vivo. To enhance the oncolytic potency of MV-Edm against radiosensitive malignancies and to facilitate noninvasive imaging of infected tissues, we generated a recombinant MV-Edm encoding the human thyroidal iodide symporter (NIS). MV-NIS replicated almost as efficiently as unmodified MV-Edm, and human tumor cells efficiently concentrated radioiodine when infected with MV-NIS. Intratumoral spread of MV-NIS was noninvasively demonstrated by serial gamma-camera imaging of iodine-123 (123I) uptake both in MV-sensitive KAS-6/1 myeloma xenografts, which regressed completely after a single intravenous dose of MV-NIS, and in MM1 myeloma xenografts, which were unresponsive to MVNIS therapy. However, MV-resistant MM1 tumors regressed completely when 131I was administered 9 days after a single intravenous injection of MV-NIS (radiovirotherapy). 131I alone had no effect on MM1 tumor growth. While the potential hematopoietic toxicity of this new therapy requires further evaluation, image-guided radiovirotherapy is a promising new approach to the treatment of multiple myeloma, an incurable but highly radiosensitive plasma cell malignancy. Testing in other radiosensitive cancers is warranted.

Animals↗

PubMed2003

Genetically targeted radiotherapy for multiple myeloma.

Multiple myeloma is a disseminated neoplasm of terminally differentiated plasma cells that is incurable with currently available therapies. Although the disease is radiosensitive, external beam radiation leads to significant toxicity due to sensitive end-organ damage. Thus, genetic approaches for therapy are required. We hypothesized that the incorporation of immunoglobulin promoter and enhancer elements in a self-inactivating (SIN) lentiviral vector should lead to specific and high-level transgene expression in myeloma cells. A SIN lentivector with enhanced green fluorescent protein (EGFP) expression under the control of a minimal immunoglobulin promoter as well as the Kappa light chain intronic and 3' enhancers transduced myeloma cell lines with high efficiency (30%-90%). EGFP was expressed at a high level in myeloma cells but silent in all nonmyeloma cell lines tested compared with the cytomegalovirus (CMV) promoter/enhancer. Transduction of myeloma cells with the targeted vector coding for the human sodiumiodide symporter (hNIS) led to hNIS expression by these cells allowing them to concentrate radioiodine up to 18-fold compared with controls. Tumor xenografts in severe combined immunodeficiency mice expressing hNIS could be imaged using iodine-123 (123I) and shown to retain iodide for up to 48 hours. These tumor xenografts were completely eradicated by a single dose of the therapeutic isotope iodine-131 (131I) without evidence of recurrence up to 5 months after therapy. We conclude that lentivectors can be transcriptionally targeted for myeloma cells and the use of hNIS as a therapeutic gene for myeloma in combination with 131I needs further exploration.

Animals↗

PubMed2003

Evaluation of a small cadmium zinc telluride detector for scintimammography.

UNLABELLED: The purpose of this study was to evaluate a small semiconductor-based gamma camera that may have applications in scintimammography. METHODS: A small cadmium zinc telluride (CZT) detector was evaluated. The detector had a field of view of 20 x 20 cm with detector elements of 2.5 x 2.5 mm in size. Both short-bore (35 mm) and long-bore (50 mm) collimators, matched to the geometry of the detector elements, were evaluated. The imaging performance of the CZT detector was compared with that of a conventional gamma camera equipped with all-purpose and ultra-high-resolution collimators. The performance of both systems with respect to breast imaging was evaluated using a water tank containing small glass spheres, 1.8-9.8 mm in diameter. The effects of variations in breast thickness, tumor depth, and tumor-to-background ratio were all simulated in this phantom model. Total counts per image were adjusted to approximate the count density observed in clinical scintimammographic studies. RESULTS: Sensitivity of the CZT detector was 76% that of the equivalent NaI system. The system demonstrated excellent integral uniformity. The energy resolution of the CZT system was 6.5% for (99m)Tc. Spatial resolution with the long-bore collimator was superior to that of a conventional large field-of -view gamma camera equipped with an ultra-high- resolution collimator, over the range 0-6 cm from the collimator face. A blinded review of breast phantom images showed that small spheres (< or =7 mm in diameter) were better seen and had a better tumor-to-background ratio with the CZT system than with the conventional gamma camera. CONCLUSION: A small CZT detector offers superior performance to a conventional gamma camera and should permit reliable detection of breast tumors <1 cm in size.

Breast↗

PubMed2002

Effects of radioisotopes on the accuracy of dual-energy X-ray absorptiometry for bone densitometry.

Nuclear medicine procedures are often performed in close-time proximity to bone densitometry studies. The purpose of this study was to determine the effects of various radioisotopes on the accuracy of bone mineral density (BMD) measurements performed using dual-energy x-ray absorptiometry (DEXA) systems. We evaluated two DEXA scanners: the Hologic QDR4500 and the Lunar Prodigy. The effects of various activities of Tc-99m, Tl-201, Ga-67 and I-131 on BMD were assessed by placing vials or syringes containing the appropriate isotope above or below a simulated spine (average BMD = 1.1 g/cm2) embedded in a lucite block. We also placed a spine phantom (average BMD = 2.0 g/cm2) in a water bath containing various concentrations of Tc-99m. Maximum activities evaluated were as follows: Tc-99m, 80 mCi; I-131, 50 mCi; Tl-201, 66 mCi; Ga-67, 20 mCi. For the Hologic QDR4500 system, irrespective of the radioisotope or activity, we found no significant effect of adjacent activity on measured BMD on this system. For the Lunar Prodigy system, the effects of adjacent activity on BMD were found to be dependent on source location, strength, and radioisotope. For sources placed beneath the solid lucite phantom, BMD decreased by approx 0.5%/10 mCi of activity for all isotopes. In general, for sources placed above the lucite phantom, the BMD decreased by 1.6-4.0%/10 mCi of activity, depending on location. The exception was Tl-201, where BMD increased by 0.5-2.5%/10 mCi, depending on location. With the high-density spine in the water phantom, the effects of adjacent activity were more pronounced than in the standard density spine in the lucite block. For a distributed Tc-99m source, the BMD decreased by 1.7%/10 mCi. The effect of radioactivity on DEXA measurements is system dependent. In general, adjacent activity results in a reduction in apparent BMD. The magnitude of the effect increases with increasing BMD and is dependent on the location of the activity.

Absorptiometry, Photon↗

PubMedDate not supplied

Combined I-124 positron emission tomography/computed tomography imaging of NIS gene expression in animal models of stably transfected and intravenously transfected tumor.

PURPOSE: With the advent of replication competent viruses for cancer gene therapy, it has become imperative to monitor the biodistribution, expression and replication of these vectors in living organisms. We evaluated the potential of I-124 positron emission tomography (PET)/computed tomography (CT) imaging in gene therapy animal models utilizing the sodium iodide symporter (NIS) and compared the findings to I-123 gamma camera imaging. PROCEDURES: CB17 SCID mice were implanted with myeloma cell lines expressing NIS or infected by MV-NIS given systemically. Mice were imaged by both gamma camera (I-123) and PET/CT (I-124 ) and image quality assessed. RESULTS: NIS expressing tumors concentrated 7.1% of the injected activity while tumors infected with the control virus had only 0.3% of the activity injected. CONCLUSIONS: I-124 PET/CT in combination with NIS allows the tracking of stably transfected tumors or intravenously transfected tumors. Combined modality imaging using PET/CT allows accurate and non-invasive imaging of the distribution and gene expression of a replicating viral vector in living systems.

Animals↗

PubMedDate not supplied

Operator-interactive method for simultaneous measurement of left and right ventricular volumes and ejection fraction by tomographic electrocardiography-gated blood pool radionuclide ventriculography.

BACKGROUND: A method that uses single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) to measure right ventricular (RV) and left ventricular (LV) volumes (in milliliters) and ejection fraction (EF) is described. METHODS AND RESULTS: We recorded 35 paired SPECT ERNA and electron beam computed tomography (EBCT) cardiac studies in 27 patients; for comparison with EBCT, a method for measurement of RV and LV volumes and EF with SPECT ERNA was developed in 18 paired studies and was validated and assessed for reproducibility in 17. Validation indicated that SPECT ERNA and EBCT were similar for measurement of RV volume (end-systolic and end-diastolic volumes in a combined analysis) and EF (180+/-74 mL vs 182+/-80 mL and 0.44+/-0.11 vs 0.43+/-0.11, respectively) and for measurement of LV volume and EF (88+/-36 mL vs 84+/-43 mL and 0.53+/-0.081 vs 0.59+/-0.07, respectively). The SPECT ERNA method was quite reproducible. CONCLUSIONS: RV and LV volumes and EF can be measured readily via SPECT ERNA.

Algorithms↗

PubMedDate not supplied

Molecular breast imaging: advantages and limitations of a scintimammographic technique in patients with small breast tumors.

Preliminary studies from our laboratory showed that molecular breast imaging (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work to a larger patient population and examines the technical factors that influence the ability of MBI to detect small breast tumors. Following injection of 740 MBq Tc-99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a lesion suspicious for malignancy that measured <2 cm on mammography or sonography. Using a small field of view gamma camera, patients were imaged in the standard mammographic views using light pain-free compression. Subjective discomfort, breast thickness, the amount of breast tissue in the detector field of view, and breast counts per unit area were measured and recorded. Follow-up was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity was 29%, 86%, and 97% for tumors <5, 6-10, and > or =11 mm in diameter, respectively. In seven patients, MBI identified eight additional mammographically occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery, there were 36 true negative and 11 false positive scans on MBI. MBI has potential for the regular detection of malignant breast tumors less than 2 cm in diameter. Work in progress to optimize the imaging parameters and technique may further improve sensitivity and specificity.

Adolescent↗