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Imaging transgene expression with radionuclide imaging technologies.

A variety of imaging technologies are being investigated as tools for studying gene expression in living subjects. Noninvasive, repetitive and quantitative imaging of gene expression will help both to facilitate human gene therapy trials and to allow for the study of animal models of molecular and cellular therapy. Radionuclide approaches using single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the most mature of the current imaging technologies and offer many advantages for imaging gene expression compared to optical and magnetic resonance imaging (MRI)-based approaches. These advantages include relatively high sensitivity, full quantitative capability (for PET), and the ability to extend small animal assays directly into clinical human applications. We describe a PET scanner (microPET) designed specifically for studies of small animals. We review "marker/reporter gene" imaging approaches using the herpes simplex type 1 virus thymidine kinase (HSV1-tk) and the dopamine type 2 receptor (D2R) genes. We describe and contrast several radiolabeled probes that can be used with the HSV1-tk reporter gene both for SPECT and for PET imaging. We also describe the advantages/disadvantages of each of the assays developed and discuss future animal and human applications.

Animals↗

The lateral view in radionuclide imaging of the sacrum.

Radionuclide bone images in the anterior and posterior views failed to demonstrate a large metastatic tumor involving the sacrum which was obvious on the lateral view. Evaluation of the sacrum by radionuclide imaging may be incomplete without the lateral projection, particularly when there is a question of false-negative anterior and posterior views or difficulty in interpreting the radionuclide images.

Adult↗

Radionuclide imaging in histiocytosis X.

Radionuclide imaging (99mTc bone scans, 99mTc S colloid scans, 99mTc brain scans and 67gallium scans) and bone radiographs were done in 54 children with histiocytosis X. The results are discussed, compared with the literature and indications for the different nuclear medicine studies are given.

Adolescent↗

Folate-receptor-targeted radionuclide imaging agents.

The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including delivery of radiolabeled folate-chelate conjugates for diagnostic imaging. This review surveys the growing literature on tumor imaging with radionuclide agents targeted to the folate receptor. Successful folate-receptor targeting has been reported, both in vitro and in vivo, using a variety of radionuclides that are suitable for clinical diagnostic imaging (67Ga, 111In, 99mTc, 66Ga, and 64Cu). While none of these agents has, to date, been demonstrated to have clinical efficacy as a diagnostic tool, existing data indicates that it is feasible to noninvasively assess (at least qualitatively) tissue folate receptor levels by external radionuclide imaging.

Animals↗

Radionuclide imaging in otolaryngology-head and neck surgery.

Radionuclide imaging provides both qualitative and quantitative information that can have dramatic effects on patient management in diseases of the head and neck. The general concepts of nuclear medicine imaging, including radiopharmaceuticals and radiation effects, are discussed. The principles and techniques of thyroid, parathyroid, bone, and salivary radionuclide imaging studies will be reviewed. The intent of this article is to provide a concise and current review of head and neck radionuclide imaging that will be useful in the day-to-day practice of otolaryngology-head and neck surgery.

Head and Neck Neoplasms↗

Evaluation of the accuracy and precision of lung aerosol deposition measurements from planar radionuclide imaging using simulation.

Planar images of known, theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies on human subjects. Total lung activity was evaluated from the simulated images together with the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image. The accuracy and precision of these measurements were calculated by comparison with the true values used in the simulation. Total activity was assessed with systematic errors within 5% and precision within 6.5%. Measured PIs varied only slowly with true PI and inter-model variation masked changes between measurements on the different distributions. The relative PI reduced inter-model variation and provided significant differences between all the distributions. PI was significantly affected by misalignment of the lung region of interest. The conducting airways deposition fraction (CADF) used in the simulation correlated linearly with the fractional activity in a central lung region, allowing CADF to be estimated with a precision of 21%.

Aerosols↗

Artificial neural network as a tool to compensate for scatter and attenuation in radionuclide imaging.

UNLABELLED: This study investigates the ability of artificial neural networks (ANN) to simultaneously correct for attenuation and Compton scattering in scintigraphic imaging. METHODS: Three sets of experiments are conducted using images of radioactive sources with various shapes and distributions in a homogeneous medium. Numerical Monte Carlo simulations and physical phantom acquisitions of radioactive geometric sources provide the basic material for correction. Our method is based on the following assumptions: information needed to correct for scattering can be extracted from the energy spectrum at each pixel without any assumption concerning the source distribution, and two diametrically opposed energy spectrum acquisitions yield enough information on the source location in the diffusing medium for simultaneous correction for attenuation and scattering. RESULTS: Qualitative and quantitative evaluations of scatter correction by ANN demonstrate its ability to perform scatter correction from the energy spectra observed in each pixel. By using the energy spectra of incident photons detected in two diametrically opposed images, multilayer neural networks are able to perform a proper restitution of projection images without any assumption on geometry or position of radioactive sources in simple geometric cases. ANN corrections compare favorably to those provided by five of the most popular methods. A satisfying correction of both scatter and attenuation is observed for a human pelvis scan obtained during routine clinical practice. CONCLUSION: An ANN is an efficient tool for attenuation and Compton scattering in simple model cases. The results obtained for routine scintigrams in a much more complex situation are strong incentives for performing further studies.

Bone and Bones↗

Evaluation of radionuclide imaging and echography in the diagnosis of thyroid nodules.

Radionuclide imaging with both Tc-99m sodium pertechnetate and Tl-201 chloride was studied in 152 patients with thyroid nodules. Ultrasonography also was performed in 81 of those patients. Tc-99m sodium pertechnetate scans demonstrated nodules in 69.7% of 78 differentiated thyroid carcinomas (DC) and 72.2% of 54 thyroid adenomas (Ad). Tl-201 chloride was accumulated in 73.7% of DC and 53.6% of Ad. By combining the Tc-99m sodium pertechnetate and Tl-201 chloride scans, the detectability of the nodules was increased to 90.8% for DC and 88.9% for Ad, respectively. The Tc-99m sodium pertechnetate scans showed better visualization of cystic lesions than did the Tl-201 chloride imaging. The Tl-201 chloride images clearly demonstrated intrathoracic tumor invasions in six cases of carcinoma and two cases of Ad. The Tl-201 chloride scan was also of value in detecting regional lymph node involvement and the recurrence and metastasis after thyroidectomy. The detectability of space-occupying lesions by ultrasonography was 96.3% in 81 patients with thyroid nodules. Ultrasonography differentiated well between solid and cystic lesions. The presence and extent of nodular lesions were detected with radionuclide imaging and ultrasonography in 98.8% of patients. Radionuclide imaging combined with ultrasonography provides a rapid, convenient, and useful method for the localization and visualization of thyroid tumors.

Adenocarcinoma↗

Comparison of color Doppler sonography and radionuclide imaging in different degrees of torsion in rabbit testes.

RATIONALE AND OBJECTIVES: We compared color Doppler sonography and radionuclide imaging in an animal model of variable torsion of the testes. METHODS: The testes of 19 rabbits with unilateral 0 degree (nontorsion), 180 degrees, 360 degrees, or 540 degrees torsion and contralateral nontorsion were evaluated by sonography serially over 24 hr. Color Doppler sonography and radionuclide imaging at 24 hr were compared and correlated with pathology in a subset of testes. RESULTS: Nontorsion (n = 16 testes) and 540 degrees torsion (n = 7 testes) were always correctly diagnosed at 24 hr by color Doppler sonography and radionuclide imaging. Torsion at 180 degrees (n = 2) was indistinguishable from nontorsion. With 360 degrees torsion (n = 6 testes), four testes had reduced or absent flow with color Doppler sonography, whereas only one testis was abnormal with radionuclide imaging. CONCLUSION: Nontorsion and extreme torsion of rabbit testes are well documented by radionuclide imaging and color Doppler sonography. Torsion at 360 degrees can result in variable flow alterations that are better detected by color Doppler sonography than by radionuclide imaging.

Animals↗

Value of radionuclide imaging techniques in assessing cardiomyopathy.

Radionuclide imaging techniques add an important dimension to the diagnosis, classification and management of myocardial disease. The gated blood pool scan provides information allowing determination of the functional type of cardiomyopathy (congestive, restrictive or hypertrophic) as well as evaluation of ventricular performance. Myocardial perfusion imaging with thallium-201 is useful in distinguishing congestive cardiomyopathy from severe coronary artery disease and also in depicting septal abnormalities in hypertrophic cardiomyopathy. Radionuclide techniques also prove useful in following progression of disease and in evaluating the efficacy of therapeutic interventions.

Cardiomyopathies↗

Radionuclide imaging of lipoma and liposarcoma.

Radionuclide imaging with technetium-99m phosphate compounds was performed in 18 patients with deep-seated soft-tissue masses. The histologically established diagnosis was intra- or intermuscular lipoma in 13 patients and liposarcoma in five. Radionuclide scans demonstrated disparate scintigraphic characteristics in these two often clinically similar lesions. Soft-tissue radionuclide accumulation occurred in two lipomas and corresponded to radiographically evident calcification. All liposarcomas were uncalcified and demonstrated intense radionuclide activity. This activity may be related to the angiographic and histologic hypervascularity of liposarcomas, which is also demonstrable on computed tomography as contrast enhancement; hence, these modalities offer the same nonspecific diagnostic information. It is concluded, however, that plain radiography and radionuclide scaning should suffice to establish the diagnosis of lipoma.

Adult↗

Osmotic blood-brain barrier disruption: CT and radionuclide imaging.

PURPOSE: To compare CT and radionuclide imaging of osmotic blood-brain barrier disruption. To develop a quantitative method for imaging osmotic blood-brain barrier disruption and to see if iopamidol could be safely given intravenously in conjunction with blood-brain barrier disruption. METHODS: Forty-five blood-brain barrier disruption procedures were imaged with CT and radionuclide scans. The scans were evaluated with visual and quantitative scales. Patients were observed for adverse effects after blood-brain barrier disruption. RESULTS: There was a 4% rate of seizures in this study. There was good agreement between visual CT and radionuclide grading systems. Quantitative methods to grade disruption did not add useful information to visual interpretations. CONCLUSIONS: Nonionic iodine-based contrast medium has a lower incidence of seizures when injected intravenously in conjunction with osmotic blood-brain barrier disruption than ionic contrast material. Contrast-enhanced CT is the preferred method to image disruption because it has better spatial resolution than radionuclide techniques.

Adolescent↗

Radionuclide imaging of miniaturized chemical analysis systems.

We propose radionuclide imaging as a valuable tool for the study of molecular interactions in miniaturized systems for chemical analysis. Sensitive and quantitative imaging can be performed with compounds labeled with short-lived positron-emitting radionuclides, such as (11)C and (68)Ga, within selected parts of the system. Radionuclide imaging is not restricted to transparent materials since the relatively energetic positrons can penetrate high optical density materials. Experimentally, a radiotracer is introduced into the object of study, which is subsequently placed on a phosphor storage plate. After exposure, the plate is scanned with a laser and a digital, quantitative image can be reconstituted. To demonstrate the concept, three types of microstructures suited for integration in chemical analysis systems were imaged with (11)C- and (68)Ga-labeled tracers. The influence of factors such as geometry of the object and type of radionuclide on resolution and sensitivity was investigated. The resolution ranged from 0.9 to 2.7 mm (fwhm). Measuring low amounts of radioactivity in the three structures, 2-20 Bq could be detected, which corresponded to 2.3-500 amol or 2.4-110 pM tracer. The imaging approach was applied to study analyte concentration and sample dilution effects on the performance of a capillary extraction column integrated in an automated LC-ESI-MS system. The utility of the technique was further illustrated by imaging of microchannels in a zeonor plastic compact disk and in a poly(dimethylsiloxane) material for the study of nonspecific peptide adsorption.

Carbon Isotopes↗

Acute testicular torsion: comparison of unenhanced and contrast-enhanced power Doppler US, color Doppler US, and radionuclide imaging.

PURPOSE: To compare the usefulness of conventional color Doppler ultrasound (US), unenhanced and contrast material-enhanced power Doppler US, and radionuclide imaging in a model of acute testicular torsion. MATERIALS AND METHODS: Twenty rabbits underwent unilateral 360 degree testis torsion and contralateral orchiopexy. Gray-scale, color Doppler, and unenhanced and contrast-enhanced power Doppler US were performed 4-6 hours later. The side of torsion was determined, and intratestis flow was graded. Within 2 hours of US, technetium-99m pertechnetate was intravenously administered, the rabbits were killed, and the testes excised for radionuclide imaging. RESULTS: Intratestis perfusion was detected in 85% of torsed testes at US and radionuclide imaging. The side of torsion was correctly diagnosed in 25% of cases with radionuclide imaging and in 60% of cases with US. Power Doppler US demonstrated significantly greater intratestis flow in pexed than in torsed testes. Although the numbers of correct diagnosis with the three US modalities were similar, flow grades within torsed and normal testes were significantly different. CONCLUSION: Perfusion to torsed and normal testes was demonstrated equally well with color Doppler US, power Doppler US, and radionuclide imaging. Doppler US better depicted differences in intratesticular flow between torsed and normal testes.

Acute Disease↗