[Show abstract][Hide abstract] ABSTRACT: The purpose of the this study was to develop an instrument for measuring the obsessive and compulsive characteristics of drinking-related thought and behavior in subjects who abuse or are dependent on alcohol, and to quantify the extent to which drinking-related thought and behavior in these subjects resemble the obsessions and compulsions seen in obsessive-compulsive disorder (OCD). To achieve these goals, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was modified to reflect obsessionality and compulsivity specifically related to heavy drinking rather than to obsessions and compulsions generally. The modified Y-BOCS (Y-BOCS-hd) was administered to 62 subjects satisfying DSM-III-R criteria for alcohol abuse or alcohol dependence and 62 matched normal controls. The data showed that the Y-BOCS-hd is a sensitive and specific instrument for measuring the obsessive and compulsive characteristics of drinking-related thought and behavior in alcohol-abusing and alcohol-dependent populations, and that there are specific and quantifiable similarities between these characteristics and the obsessions and compulsions of OCD. The data also indicated that the Y-BOCS-hd may be a useful screening instrument for the presence of alcohol abuse and dependence.
Alcoholism Clinical and Experimental Research 04/2006; 16(2):266 - 271. · 3.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The uptake of fluorine-18 fluorodeoxyglucose (F-18 FDG) by a malignant tumor depends on the blood glucose level. The authors present a striking case that illustrates the importance of blood glucose measurement in F-18 FDG positron emission tomographic (PET) imaging in a patient with a solitary pulmonary nodule. With the emergence of freestanding imaging centers, this case emphasizes the importance of using an objective method, such as a glucometer, to measure blood glucose levels before F-18 FDG PET imaging. Results of the initial scan were equivocal (the patient had eaten before the scan), whereas a hypermetabolic focus was clearly identified on a second scan obtained 2 days later.
Clinical Nuclear Medicine 12/2001; 26(11):908-9. · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gene therapy trials for ovarian cancer would benefit from a noninvasive imaging modality to detect the location and extent of gene transfer. The human type 2 somatostatin receptor gene (hSSTr2) was evaluated as a reporter gene for imaging adenoviral (Ad) gene transfer to ovarian cancer.
A replication-incompetent Ad vector encoding hSSTr2 (Ad-hSSTr2) was used to infect SKOV3.ip1 cells in vitro and tumors growing in nude mice. Gamma camera imaging detected uptake of 99m-Tc-P2045 (a somatostatin analogue) due to expressed hSSTr2.
Specific uptake of 99m-Tc-P2045 was imaged in Ad-hSSTr2-infected cells in vitro. Noninvasive in vivo imaging detected gene transfer to intraperitoneal tumors. Uptake of 99m-Tc-P2045 (percentage dose per gram of tumor) averaged 2.2 and 0.18 for Ad-hSSTr2-injected mice and controls, respectively.
This study reports the first noninvasive imaging method for imaging gene transfer to ovarian cancer. A human gene therapy trial is planned.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to develop a sensitive, noninvasive imaging method for monitoring ovarian xenografts during therapeutic intervention.
Human ovarian tumor cells (SKOV3.ip1) were infected with a replication-deficient adenoviral (Ad) vector encoding green fluorescent protein (GFP). The GFP-positive tumor cells were imaged in vitro and in vivo with a fluorescence stereomicroscope. Using appropriate filters, both GFP fluorescence and adriamycin were simultaneously detected. Nude mice implanted with GFP-positive cells were imaged repeatedly, in a noninvasive manner.
SKOV3.ip1 cells infected with Ad-GFP showed high GFP fluorescence, which was eliminated after treatment with adriamycin. Loss of GFP fluorescence was confirmed to be dead cells. For in vivo imaging, intraperitoneal tumors as small as 0.2 mm in diameter were detected externally. Adriamycin uptake was detected in tumors by in vivo imaging, and reduction in tumor size was concurrent with decrease in GFP fluorescence. These findings were confirmed at necropsy.
Fluorescence stereomicroscopy monitored the response of ovarian xenografts to adriamycin therapy. For the first time, GFP and adriamycin were imaged simultaneously.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this work was to develop a high capacity method to image gene transfer to cancer cells growing as monolayers in cell culture plates. A sensitive and high capacity nuclear-imaging method for detection of gene transfer in vitro will allow rapid validation of vectors in different cell lines under various conditions. Human cancer cell lines (A-427 non-small cell lung, SKOV3.ip1 ovarian, MDA-MB-468 breast, and BxPC-3 pancreatic) were infected with a replication-incompetent adenoviral vector encoding the human type 2 somatostatin receptor (Ad-hSSTr2). Expression of the hSSTr2 reporter protein in cells was detected by imaging an internalized 99mTc-labeled, hSSTr2 binding peptide (P2045, Diatide, Inc.). Imaging provided an accurate measure of internally bound 99mTc as evidenced by equivalence of results for imaging region of interest (ROI) analyses and gamma counter measurements. Internally bound 99mTc-P2045 was linearly correlated (R2 = 0.98) with the percentage of hSSTr2-positive cells following gene transfer. Excess P2045 blocked binding and internalization of the 99mTc-P2045, indicating the specificity of the technique. Up to four 96-well plates could be imaged simultaneously, thereby demonstrating the high capacity of the system. This novel in vitro approach provides a new method to test enhanced gene transfer as new vectors are developed.
[Show abstract][Hide abstract] ABSTRACT: A gamma camera imaging method was developed to detect dual gene transfer to adherent cells growing as monolayers in cell culture plates. Human cancer cells were infected with replication-incompetent adenoviral vectors encoding the human type 2 somatostatin receptor (Ad-hSSTr2) and/or herpes virus thymidine kinase (Ad-TK). The hSSTr2 and TK reporter proteins were detected by imaging internally bound (99m)Tc-P2045 peptide (Diatide, Inc.) and radioiodinated 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively. Following gene transfer, expression of hSSTr2 and TK were accurately imaged in vitro.
Nuclear Medicine and Biology 03/2001; 28(2):135-44. · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of Tc-99m sestamibi to localize parathyroid adenomas is well established. Its greatest value is in the detection of adenomas in presurgical candidates to localize one or more adenomas in the parathyroid glands or to identify ectopic parathyroid adenomas. The authors describe a patient who had long-standing hyperparathyroidism with a history of end-stage renal disease, hypertension, and peptic ulcers with gastrointestinal bleeding. The scan showed a large ectopic parathyroid adenoma in the left retrosternocleidomastoid region. At surgery, the adenoma was located between the jugular vein and the carotid artery, within the carotid sheath.
Clinical Nuclear Medicine 02/2001; 26(1):27-8. · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gene therapy protocols require better modalities to monitor the location and level of transferred gene expression. One potential in vivo mechanism to assess gene expression would be to image the binding of a radiolabeled peptide to a reporter receptor that is expressed in targeted tissues. This concept was tested in a tumor model using a replication-incompetent adenoviral vector encoding the human type 2 somatostatin receptor (Ad5-CMVhSSTr2). Expression of the hSSTr2 reporter was imaged using a radiolabeled, somatostatin-avid peptide (P829).
Bilateral subcutaneous A427 tumor xenografts were established on the flanks of athymic nude mice. These human-origin, non-small cell lung tumors are normally negative for hSSTr2 expression. One tumor was injected directly with Ad5-CMVhSSTr2, whereas the second tumor was injected directly with a control Ad5 vector. The mice were injected intravenously 48 h later with P829 peptide that was radiolabeled to high specific activity with 99mTc (half-life, 6 h) or 188Re (half-life, 17 h). Tumors were frozen and evaluated for somatostatin receptor expression using fluorescein-labeled somatostatin.
The accumulation of radiolabeled P829 in hSSTr2-expressing tumors was easily visualized by gamma camera imaging 3 h after injection. Imaging region of interest analyses and biodistribution studies confirmed a 5- to 10-fold greater accumulation of both radiolabeled P829 peptides in the Ad5-CMVhSSTr2-injected tumors versus control tumors injected with control Ad5 vectors. Ad5-CMVhSSTr2-injected tumors accumulated 2.5-3.8 percentage injected dose per gram 3 h after injection. Only Ad5-CMVhSSTr2-injected tumors expressed somatostatin receptors, as determined by immunohistochemistry.
These studies show the feasibility of imaging a 99mTc-labeled peptide's binding to a reporter receptor after in vivo gene transfer to tumor cells. The 188Re-labeled peptide worked equally well for this imaging approach and offers the additional advantage of energetic beta decay with potential therapeutic efficacy. 99mTc and 188Re are generator produced, an advantage for widespread availability and low cost, and both radioisotopes can be imaged with existing, high-resolution modalities. There is great potential for using 99mTc-labeled peptides for imaging gene transfer with the hSSTr2 reporter receptor, especially when the reporter correlates with the expression of therapeutic genes that can be included simultaneously in the gene therapy vector.
Journal of Nuclear Medicine 06/2000; 41(5):887-95. · 5.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this report is to demonstrate the utility of ictal brain single photon emission tomography (SPECT) in a 39-year-old man with complex partial seizures arising from the anterior cingulate gyrus. Seizures originating from the anterior cingulate gyrus are difficult to localize because they have variable ictal semiology, are usually brief, and have rapid cortical propagation.
Clinical neurologic examination, electroencephalography, extended video-electroencephalography with scalp and sphenoidal electrodes, magnetic resonance imaging, computed tomography, and ictal brain SPECT with Tc-99m HMPAO were performed to identify the seizure focus. The patient's regional cerebral blood flow (rCBF) findings were compared with those of eight normal controls, and changes in rCBF were assessed by comparing the patient's ictal scan with those of normal controls at rest by using statistical parametric mapping (SPM).
Clinical and neurologic evaluations failed to demonstrate the epileptogenic focus. Ictal rCBF brain SPECT showed a focal region of hyperperfusion in the anterior cingulate gyrus. By using SPM, the ictal blood flow increase in the right anterior cingulate gyrus (x, y, z, -6, 42, 24 mm) was found to be statistically significant when compared with normal controls (z score, 4.88, p < 0.001). Subdural EEG recordings with intracranial electrodes positioned over this location confirmed that the cingulate gyrus was the origin of the seizures, and surgical resection resulted in >90% seizure reduction.
We concluded that ictal brain SPECT localization in conjunction with subdural electrode confirmation is a useful test in the presurgical evaluation of difficult to localize cingulate epilepsy.
[Show abstract][Hide abstract] ABSTRACT: This paper examines the use of neuroimaging to measure change in regional cerebral blood flow (rCBF) produced by pain in patients with fibromyalgia and in healthy individuals. Fibromyalgia patients differ from healthy persons in rCBF distribution in several brain structures involved in pain processing and pain modulation both at rest and during experimental pain induction. These abnormalities may contribute to abnormal pain sensitivity as well as the maladaptive pain behaviors that characterize many patients with fibromyalgia. We anticipate that future neuroimaging studies will enhance our understanding of abnormal pain sensitivity and of pain management interventions aimed at altering central nervous system function in patients with fibromyalgia.
Current Rheumatology Reports 05/2000; 2(2):141-8. · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary progressive aphasia (PPA) is an uncommon degenerative dementia characterized by gradual impairment of language function with initial sparing of the memory domain. Using semiquantitative 99mTc-hexamethyl propyleneamine oxime (HMPAO) brain SPECT as a measure of regional cerebral blood flow (rCBF), we investigated the relationship between reduced 99mTc-HMPAO uptake and the severity of dysnomia in PPA.
Seven right-handed patients with PPA had their dysnomia assessed by the Boston Naming Test (BNT), a subtest of the Boston Diagnostic Aphasia Examination. Neuroimaging studies, including 99mTc-HMPAO brain SPECT, CT, and MRI, were performed. Correlational analysis between reduced rCBF and BNT was performed.
Brain SPECT showed a reduction in 99mTc-HMPAO uptake involving the frontal and temporal lobes in all 7 patients. CT and MRI showed mild to moderate cerebral atrophy in 4 patients. Low scores on the BNT correlated with low frontotemporal 99mTc-HMPAO (Spearman r = 0.97, P = 0.004) in the 5 patients with left-hemisphere involvement.
Decreased rCBF to the frontotemporal region characterized the cerebral abnormalities associated with PPA. The finding of focal rCBF abnormalities in the right hemisphere of 2 right-handed women corroborates that PPA symptoms may arise from a "non-left-dominant"-hemisphere degenerative process. Our results support the usefulness of rCBF SPECT imaging as a diagnostic aid in PPA.
Journal of Nuclear Medicine 03/2000; 41(2):228-33. · 5.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We describe a new method for measuring brain tumor uptake of TI-201 and Tc-99m sestamibi (MIBI) that permits the semiquantitative comparison of tracer uptake to yield comparable "tumor bulk" ratios. We tested this method in patients treated recently and remotely with chemotherapy to determine if this method could identify differences between these two patient groups.
Eleven patients with high-grade astrocytoma underwent TI-201 and Tc-99m MIBI SPECT. Each patient received 5 mCi TI-201 intravenously followed by SPECT using a dual-head gamma camera. This was immediately followed by an intravenous injection of 20 mCi Tc-99m MIBI and repeated SPECT. Four patients had recent therapy (from 1 day to 6 weeks before SPECT) and seven had remote treatment (>1 year before SPECT). Regions of interest were outlined in the tumor area using a computer-automated program to include all counts above background activity. Tumor activity counts were obtained from this region of interest. The tumor region of interest was mirrored to the contralateral uninvolved cerebral hemisphere to obtain background control count activity. A hypothetical volume of the number of pixels with background count activity necessary to constitute the tumor count activity (tumor bulk) was calculated using the ratio of total tumor counts (Ct), subtracting background (Cb), and dividing by the average counts per pixel in the control region (Cab). This was multiplied by the number of pixels (P), the pixel volume (Vp), and summed over all sections (i) involved with tumor. This method yields the equation tumor bulk =
The mean Tc-99m MIBI to TI-201 tumor bulk ratio was 1.03 (range, 0.81 to 1.12) in four patients who had recently received chemotherapy. The mean Tc-99m MIBI to TI-201 tumor bulk ratio was 1.55 (range, 1.46 to 1.64) in seven patients who had remote therapy. The difference in the Tc-99m MIBI to TI-201 tumor bulk ratio between the two groups was significant (P = 0.0001). Patients who received recent chemotherapy had relatively lower Tc-99m MIBI uptake compared with TI-201. In remotely treated patients, uptake of the Tc-99m MIBI was greater compared with TI-201.
This method allows semiquantitative comparison of different tracer uptake values independent of tracer dose and reduces the variability in drawing a region of interest when measuring tumor uptake. Among the patients studied, those who had recent chemotherapy showed a low Tc-99m MIBI to TI-201 ratio. This method of measuring "tumor bulk" can provide a useful index of viable tumor size in evaluating early tumor response and during ongoing chemotherapy.
Clinical Nuclear Medicine 11/1999; 24(11):868-73. · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the potential of an E-selectin-binding peptide (ESbp) to specifically bind activated endothelium in rheumatoid arthritis (RA) animal models.
ESbp (KYDGDITWDQLWDLMK; 2,027 daltons) was labeled with biotin and 99mTc. The affinity of ESbp derivatives for E-selectin was measured by enzyme-linked immunosorbent assay. The binding of biotin-ESbp was compared with that of an anti-E-selectin antibody, by immunohistochemical analyses of human synovial sections and sections from the Mycoplasma pulmonis MRL-lpr/lpr mouse arthritis model. 99mTc-ESbp was sequentially imaged in vivo with a gamma camera in the rat adjuvant-induced arthritis model.
E-selectin expression was detected in human RA synovium and mouse arthritic synovium using biotin-ESbp. Both biotin-ESbp and 99mTc-labeled ESbp had high affinity for E-selectin (dissociation constant 2-5 nM). In vivo imaging showed specific binding of 99mTc-ESbp to the rat ankle joint prior to clinical manifestations of inflammation.
These results demonstrate that activated endothelium can be targeted with 99mTc-ESbp. The specificity of targeting can be used to evaluate up-regulation of E-selectin in RA models, and to follow changes in this up-regulation during treatment trials.
[Show abstract][Hide abstract] ABSTRACT: In vivo counting with the use of a germanium detector evaluated the retention of an elemental 59Fe powder supplement while measuring potential interactions with zinc, calcium and copper. Effects of dietary iron and zinc on in vivo retentions of 59Fe, 65Zn, 67Cu and 47Ca were studied in young pigs. In Experiment 1, 4-d-old piglets fed a cereal-based diet were randomly assigned to one of four treatment groups (2 x 2 factorial arrangement, n = 5 per group). Variables were dietary iron source (either elemental iron or FeSO4, each at 100 mg iron/kg diet) and the dosage form of radioactive iron (either elemental 59Fe powder or 59FeSO4). Experiment 2 (2 x 3 factorial arrangement) was performed using two levels of iron (100 and 200 mg/kg, as elemental iron) and three levels of zinc (25, 50 and 100 mg/kg). Piglets were also dosed with 47Ca, 65Zn and 67Cu; all radioisotopes were measured for 8 d. Apparent absorption of elemental 59Fe powder was 13 +/- 1%, whereas 59Fe sulfate was significantly (P < 0.05) higher at 26 +/- 1%. The FeSO4 diet decreased 65Zn retention in Experiment 1, in contrast to the elemental iron diet, which did not have this effect in either experiment. Apparent 65Zn absorption averaged 44 +/- 2, 35 +/- 1 and 27 +/- 2% for the three levels of zinc (25, 50 and 100 mg/kg), respectively. Retention of 47Ca was not affected by dietary iron or zinc; retention of 67Cu was not affected by dietary iron. The data demonstrate good bioavailability of elemental iron without effects on zinc, copper and calcium.
Journal of Nutrition 01/1999; 129(1):181-7. · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To understand the relationship of caudate, thalamic, and anterior cingulate perfusion to pain states, we investigated familial restless legs syndrome in a father and daughter during the state of pain induced by immobility using semiquantitative regional cerebral blood flow (rCBF) brain single photon emission computed tomography (SPECT). The father underwent 4 brain SPECT scans using the rCBF tracer 99mTc-HMPAO several weeks apart, at different pain levels and after treatment with L-dopa. Caudate, thalamic, and anterior cingulate rCBF indices were measured. The caudate nuclei showed a 13% reduction in rCBF with increasing pain. The thalami and anterior cingulate showed a 7 and 6.6% increase in rCBF, respectively, with increasing pain. Compared to normal controls at rest, there was a decrease in caudate rCBF by 13% and an increase in thalamic rCBF by 3%. Linear regression for the caudate nuclei revealed a significant reduction in rCBF (p < 0.05), as pain increased. The daughter underwent an identical rCBF brain SPECT scan procedure at a high pain level induced by immobilization. Her scan showed a 12% reduction in caudate rCBF and a 1.2% increase in the anterior cingulate rCBF compared to healthy controls. The study supports the association between pain and decreased regional cerebral blood flow to the caudate nucleus as reported in fibromyalgia syndrome. There is increase in anterior cingulate rCBF with increasing pain. Our findings also corroborate that there is increased thalamic rCBF with pain stimulation.
The Journal of Rheumatology 12/1998; 25(11):2270-5. · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatic sequestration of systemically administered adenoviral vectors reduces the number of viral particles available for delivery to other tissues. The biological basis of this phenomenon was investigated using a new in vivo technique which permitted imaging in real time. Recombinant adenovirus serotype 5 knob (Ad5K) was radiolabeled with the gamma-emitter 99mTc (half-life = 6 h). Scatchard analysis of the 99mTc-Ad5K showed specific, high-affinity binding to U293 cells (Kd = 1.4 +/- 0.5 nM), demonstrating that the radiolabeling process had no effect on receptor binding. In vivo dynamic imaging with an Anger gamma camera revealed that the liver binding followed an exponential rise to maximum, with a measured 100% extraction efficiency. Initially, the liver binding capacity was 3.1 +/- 0.4 micrograms Ad5K, equivalent to approximately 17,000 Ad5K molecules per liver cell. Liver binding was blocked by preincubation of Ad5K with neutralizing anti-Ad5K antibody; a 50% reduction in liver uptake was demonstrated by imaging. Unlabeled Ad5K was more effective in blocking liver uptake of 99mTc-Ad5K, whereas irrelevant unlabeled Ad3K had no effect. Imaging data for the liver uptake studies were in agreement with biodistribution determined by removing and measuring tissues. These data demonstrated that in vivo imaging is a sensitive tool for measuring changes to liver tropism. Similar imaging techniques can be applied to adenovirus vectors to measure specific targeting for gene therapy.
[Show abstract][Hide abstract] ABSTRACT: The evaluation of pain is one of the major problems facing general practitioners and specialists in medicine. Although the source of pain can be usually be traced to specific abnormalities in a given organ system, some patients present with generalized pain syndromes, such as fibromyalgia, for which no specific source can be found. Some researchers have begun to consider that although there may be a somatic source of such pain at its initiation, over time the pain may be maintained or exacerbated by functional alterations in critical regions of the brain and spinal cord that are involved in pain processing or pain inhibition. This article describes the techniques currently used to measure regional cerebral blood flow (rCBF) in the brain by single photon emission computed tomography (SPECT) imaging, and reviews the SPECT and positron emission tomography literature concerning alterations in functional brain activity associated with pain in healthy individuals and in patients with chronic pain, including those with fibromyalgia. The article concludes by describing the implications of current knowledge about pain and abnormal functional brain activity in the understanding of the pathophysiology of fibromyalgia and in the development of therapeutic strategies to manage patients with this disorder.
The American Journal of the Medical Sciences 07/1998; 315(6):385-96. · 1.52 Impact Factor