Utilization of parasternal lymphoscintigraphy in radiation therapy of breast carcinoma.

In radiation therapy of patients with breast carcinoma, the ipsilateral internal mammary lymph nodes are either irradiated by a separate anterior field or included by isocentric opposing tangential fields, which also treat the breast and chest wall. To determine the acceptability of a particular treatment setup, the positions of the nodes must be determined with respect to the treatment fields. For the anterior field technique the problem is two-dimensional and is solved by simply superimposing the treatment field onto an anterior lymphoscintigram. For treatment by opposing tangential fields the problem is three-dimensional and more complex. The solution described in this note is to project the three-dimensional lymph node positions, obtained by a stereo-lymphoscintigraphic procedure, onto the tangential field radiographs. A mathematical expression is given to perform the required projection of the node positions onto the radiographs.

Metabolism of 99mTc-L,L-ethyl cysteinate dimer in healthy volunteers.

99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products.

A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain.

The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.

Improved performance from modifications to the multidetector SPECT brain scanner.

A multidetector single photon emission computerized tomographic brain scanner was modified to improve the angular sampling. The detector plate was rotated such that 12, 24, or 36 angular projections could be acquired. Phantom experiments demonstrated that the angular aliasing artifacts seen in images obtained with 12 detectors were eliminated with 36 effective detectors. In addition, the reconstructed image noise in a uniform source was decreased by a factor of 1.7 by the use of 36 instead of 12 angular projections, as predicted by computer simulation.

Limitations of dual-photopeak window scatter correction for brain imaging.

UNLABELLED: A method for performing scatter corrections that would directly use the photopeak information and would be straightforward for use in clinical practice would be attractive in SPECT imaging. The dual-photopeak window method may be such a method. It relates the scatter fraction to the ratio of the lower to the total parts of a split-photopeak window. We investigated the use of this scatter correction method on a dedicated brain camera. METHODS: Calibration curves for the Ceraspect, a dedicated brain imaging camera, were obtained for four split-window combinations using point sources in air and water. Simulations of the Ceraspect calibration curves at several energy resolution values were obtained using a Monte Carlo simulation of the instrument. RESULTS: The calibration curves, experimental and simulated, revealed an ambiguous and unstable relationship between lower-to-total ratio and scatter fraction. CONCLUSION: The unsatisfactory calibration curves can be attributed to the limited scatter produced in a brain-sized phantom during the calibration process and inherent stability problems in the calibration process. The dual-photopeak window method is not usable for small-field imaging systems and may even be unstable for larger-field systems.

Characteristics of a scanning, multidetector, single-photon ECT body imager.

We evaluated a single-photon emission computed tomographic system using ten scanning detectors in a circular array. The system uses focusing collimators that scan radially as well as tangentially. The spatial resolution in the tomographic plane is 2.6 cm FWHM and the axial resolution is 3.3 cm FWHM. The resolution is independent of position within the field of view, and nearly independent of energy through 511 keV. Sensitivity was found to be 4600 cps/muCi-ml for an extended phantom, 20-cm in diameter, filled with Tc-99m; 7200 cps/muCi-ml with TI-201; and 8000 cps/muCi-ml with Ga-67. Investigations of positional uniformity indicated some quantitative distortion of data due to inadequate attenuation correction. Improvement in the attenuation correction is necessary before truly quantitative tracer distribution studies are undertaken.

The application of internal mammary lymphoscintigraphy to planning of radiation therapy.

A technique is described for the anterior and lateral imaging of the thorax during internal mammary lymphoscintigraphy. It permits reliable estimates of lymph-node location to within 3 mm of the actual location. Use of the results from these measurements can be directly applied to radiation portal planning.

Tantalum-178-labeled agents for lung and liver imaging.

Despite its 9.3-min half-life, Ta-178 can be used to produce radiopharmaceuticals for lung and liver imaging. A variety of human serum albumin microspheres and other particulate radiopharmaceuticals were labeled with Ta-178. A period of approximately 10 min was required for their preparation and administration to rats. Extrapolation to the clinical situation suggests that imaging could take place after one half-life of the nuclide has elapsed. We found that satisfactory imaging is possible using Ta-178 radiopharmaceuticals with the Anger camera and a pinhole collimator. Since short imaging times, high spatial resolution, and low patient doses are reasonable objectives in pediatric scintigraphy, these new radiotracers may prove useful for lung and liver imaging in children.

Scintigraphic imaging with tantalum-178 and the Anger scintillation camera: concise communication.

Tantalum-178 is a short-liver radionuclide (T 1/2 = 9.3 min.) and emits primarily 56- to 64-keV characteristic x-rays. We have determined the imaging characteristics with this radionuclide and a large-field-of-view Anger camera. With a pinhole collimator, good spatial resolution is possible with Ta-178, although the image quality is superior with Tc-99m under comparable conditions. Spatial resolution with parallel-hole or converging collimators was much less satisfactory with Ta-178 because of septal penetration by high-energy photons. Pulmonary perfusion and liver-spleen images of excellent quality were obtained in the rabbit using the pinhole collimator and Ta-178-labeled agents.

Pediatric applications of pinhole magnification imaging.

Pinhole magnification imaging is an important technique for practitioners of pediatric nuclear medicine. This article reviews basic principles of pinhole magnification imaging and ways for optimizing image acquisition with this technique. Applications to skeletal scintigraphy, scrotal scintigraphy and renal cortical scintigraphy are discussed and illustrated.

Biodistribution and dosimetry of N-isopropyl-p-[123I]iodoamphetamine in the primate.

The biodistribution of N-isopropyl-p-[123I]iodoamphetamine (I-123 IMP) in the Macaca fascicularis monkey was determined at 15 min and at 1, 4, 24, and 48 hr after intravenous injection. Brain uptake was 7.8% of the injected dose at 1 hr, with little change in concentration between 15 min and 1 hr, falling thereafter. Eye uptake reached a maximum of 0.23% of injected dose at 24 hr, with activity primarily in the pigmented layers. The human absorbed radiation dose was calculated on the basis of biodistribution data. The critical organ is the eye (0.407 rad/mCi of I-123 IMP). The eye dose increased to 1.11 rad/mCi with 4% contamination from I-124 IMP and to 0.535 rad/mCi with 0.4% contamination from I-125 IMP. The absorbed dose to the liver was 0.127 rad/mCi for pure I-123 IMP and the thyroid dose was 0.120 rad/mCi, both increasing with either I-124 or I-125 contamination. While delayed eye uptake has not yet been reported in the human, care should be exercised in limiting the amount of contaminating I-124 or I-125 to the lowest practical level.

Extracranial metastatic glioblastoma: appearance on thallium-201-chloride/technetium-99m-HMPAO SPECT images.

Sequential thallium-201-chloride and technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) images were obtained in a patient with extracranial metastatic glioblastoma multiforme. Thallium-201 uptake was high (three times the scalp background) in all pathologically confirmed extracranial metastases and moderate (1.6 times scalp background) intracranially, where most biopsy specimens showed gliosis with scattered atypical astrocytes. Technetium-99m-HMPAO uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated. It was also decreased in one well-encapsulated scalp lesion and high in another scalp mass with less defined borders. Possible mechanisms of tumor uptake of these agents are reviewed.

Single-photon transaxial emission computed tomography of the heart in normal subjects and in patients with infarction.

Resting computerized transaxial tomography was performed after the i.v. injection of thallium-201 in six normal subjects and in five patients who had had myocardial infarctions 3 mo to 4 yr before scintigraphy. Decreased myocardial activity corresponded to the site of previous infarction in all cases and was clearly separated from adjacent myocardium with normal activity. With tomography, the left ventricle was clearly separated from surrounding structures such as the left-ventricular cavity, the lungs, and the liver. This study demonstrates the feasibility for the assessment of myocardial perfusion using single-photon transaxial emmission computed tomography.

Brain perfusion SPECT using an annular single crystal camera: initial clinical experience.

The annular single-crystal brain camera (ASPECT) is a digital SPECT system with a single-crystal sodium iodide thallium Nal(Tl) ring detector and collimator system designed to view the patient's head from three angles simultaneously. The ring is rotated concentrically to the detector for three-dimensional reconstruction over a 21.4 cm (diameter) by 10.7 cm (length) field of view. We evaluated the system clinically by imaging a Hoffman brain phantom and seven subjects, of whom two were normal controls, three had previous cerebral infarction and two had dementia. The ASPECT system produced tomographic images of high spatial resolution. In normal subjects, the separation of striata from thalami by the posterior limbs of the internal capsules was much clearer on ASPECT images than on rotating gamma camera images. The high spatial resolution obtained with the ASPECT system translates into superior anatomical representation of the brain compared to the standard rotating gamma camera.

Quantification of flow in a dynamic phantom using Rb81-Kr81m, and a Nal detector.

Blood flow can be measured by monitoring the count rate of Krypton-81m after its parent, Rubidium-81 (a potassium analogue), has been deposited in the tissue. The steady-state Kr-81m count rate reflects both production by decay of Rb-81 and washout due to blood flow. Its use is theoretically superior to that of Xenon-133 for quantification of blood flow (cc/min per 100 gm) since: (1) multiple flow measurements can be obtained from a single arterial injection, (2) flow-dependent changes in the count rate of Kr-81m provide a steady-state measure of specific flow, and (3) errors due to uptake in fat are eliminated. The count rate of Kr-81m was measured as a function of flow in a dynamic phantom with a NaI crystal, suing both pure cyclotron-produced Rb-81 and commercially available samples with as much as 25% contamination from Rb-82m. The phantom was calibrated by measuring the flow-rate constants with Xe-133. No significant difference was found between the flow-rate constant measured with three pure samples. The ratio of the zero-flow Kr-81m count rate to the rate observed in the presence of flow showed excellent correlation with calibrated flow over a range of rate constant from 0 to 0.02 sec (-1). This study suggests that regional specific flow can be measured in vivo with currently available Nal detecting systems after the intra-arterial injection of Rb-81.

Radionuclide left ventriculography with the slant hole collimator.

A 30 degrees slant-hole collimator was used during radionuclide ventriculography of the cardiac blood pool to improve imaging of the heart in both the modified left anterior oblique (MLAO) and right anterior oblique (RAO) views. In the MLAO view, with the holes slanted caudally, good separation between the left atrium and left ventricle was achieved, and the septum was displayed without foreshortening. In the RAO view with the collimator flat against the chest there was better resolution of the cardiac apex. The results of ejection fraction and wall motion analysis in these patients correlated well with contrast ventriculography (r=0.94). Combination of the slant-hole collimator, in vivo red blood cell labeling with stannous pyrophosphate, simultaneous collection of all phases of the cardiac cycle, and cine mode display, provide a practical system for the noninvasive measurement of left ventricular performance parameters.

Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain.

A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy.

Technetium-99m ECD: a new brain imaging agent: in vivo kinetics and biodistribution studies in normal human subjects.

Lipophilic neutral 99mTc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, 99mTc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of [99mTc]ECD showed that the maximum 99mTc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of 99mTc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of [99mTc]ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of [99mTc]ECD. These results show that [99mTc]ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.

Initial experience with SPECT (single-photon computerized tomography) of the brain using N-isopropyl I-123 p-iodoamphetamine: concise communication.

Forty-six patients were studied with N-isopropyl I-123 p-iodoamphetamine (IMP) and the Harvard Scanning Multidetector Brain System. In nine control patients, good differentiation between the gray and white matter of the cerebral cortex and the basal ganglia was evident. Regional uptake was affected by physiologic maneuvers (visual stimulation). In 24 patients studied for stroke, IMP images demonstrated areas that were involved in acute infarction in eight patients whose initial transmission computerized tomography (TCT) was normal; IMP also showed perfusion abnormalities larger than the TCT abnormality in ten patients. Perfusion abnormalities were present in 23/24 of these patients. Seven patients studied with a history of TIA had normal TCT and IMP images. In three patients studied during seizure activity, regions of hyperperfusion corresponded to the EEG seizure focus. Markedly decreased activity was present in three patients with brain tumor and corresponded to the focal abnormality on the TCT study. Our study demonstrates the feasibility of assessing regional brain perfusion using a radiopharmaceutical that is lipid soluble and has a high extraction fraction in the brain, together with single-photon ECT.

Intratumoral administration of 5-[123I]iodo-2'-deoxyuridine in a patient with a brain tumor.

UNLABELLED: We have initiated a study in which patients suspected of having primary gliomas are given a single intracerebral injection of the thymidine analog 5-[123I]iodo-2'-deoxyuridine ([123I]IUdR). The purpose of the study is to determine the biodistribution of the radiopharmaceutical and to calculate dose estimates to the tumor and normal tissues. METHODS: A patient with a cystic glioma was injected with [123I]IUdR. Whole-body scans and brain scans were obtained at various times after injection, and blood, urine and stools were collected and assayed for radioactivity to assess its biodistribution and clearance. RESULTS: Scintigraphic imaging demonstrated that the distribution of radiolabeled IUdR was mainly confined to the tumor (injection site), stomach and bladder. Disappearance from the tumor site and blood clearance were delayed probably due to collection in the cystic lesion. Eighty percent of the injected dose was recovered in the urine. CONCLUSION: The pharmacokinetics of [123I]IUdR locoregionally administered to a human glioma in situ resembled those observed in a rat glioma model where administration of the radiopharmaceutical radiolabeled with the Auger electron emitter 125I was therapeutically effective.