Showing papers in "The Journal of Nuclear Medicine in 1981"

Myocardial Imaging with a Radioiodinated Norepinephrine Storage Analog

Abstract: Meta-iodobenzylguanidine (M-IBG), an iodinated aromatic analog of the hypotensive drug guanethidine, localizes in the heart of the rat, dog, and rhesus monkey. A comparative study of tissue distribution in the dog has been performed with five myocardiophilic agents: thallium-201, I-125 16-iodohexadecanoic acid, H-3 norepinephrine, C-14 guanethidine and I-125 M-IBG. The last two compounds give heart concentrations and heart-to-blood concentration ratios similar to those of thallium-201. Planar and tomographic images of the hearts of the dog and rhesus monkey were obtained using I-131 or I-123 labeled M-IBG. Blocking studies with reserpine suggest that a major component of myocardial retention of M-IBG is sequestration within the norepinephrine storage vesicles of the adrenergic nerves. The localization of M-IBG in other organs with rich sympathetic innervation and the relative insensitivity of myocardial uptake to a wide range of loading doses lend additional support for a neuronal mode of retention.

Myocardial imaging in man with I-123 meta-iodobenzylguanidine.

Abstract: Meta-(/sup 123/I)iodobenzylguanidine (m-(/sup 123/I)IBG), a guanethidine analog, was used to image the myocardium in five normal male volunteers. Each subject received 2.0 mCi m-(/sup 123/I)IBG intravenously. Four were given a bolus injection. Multiple myocardial scintigrams were obtained over a 2-hr period. Myocardial uptake was calculated by dividing the decay-corrected global myocardial count rate (after interpolated background correction) by the peak count rate during the first passage of the m(/sup 12/3I)IBG bolus through the heart. The left ventricle could be visualized within 1 to 2 min of m-(/sup 123/I)IBG injection. Mean myocardial uptake was 0.63% (range 0.45 to 0.78%) of injected dose at 5 min, and 0.76% (range 0.49 to 0.93%) at 2 hr (n = 4). m-(/sup 123/I)IBG may provide quantitative information on myocardial catecholamine content.

Spatial and temporal quantitation of plane thallium myocardial images.

Abstract: A computer method has been developed to determine the relative initial uptake and segmental washout rates of thallium-201 from sequential myocardial images. Initial images in multiple projections are obtained at 10 min after thallium-201 injection, and delayed images 2-3 hr after injection. A modified interpolative method was used to construct a background reference plane, and net myocardial counts was used to construct a background reference plane, and net myocardial counts above this reference plane were determined from multiple count profiles. Washout rates were determined by linear regression of time-activity curves constructed from the sequential images. In this approach, both relative temporal as well as relative spatial quantitation is performed. Data from 25 normal subjects were used to establish numerical criteria and normal ranges for relative focal defects and abnormal segmental washout slopes. Normal ranges were set to include the 90-percentile limits of the distribution of values obtained from the normal population. From these values we derived a quantitative criterion for thallium scan interpretation that can be used for analysis and interpretation of scintigrams in clinical situations.

Quantitative thallium-201 exercise scintigraphy for detection of coronary artery disease.

Abstract: In 140 patients with chest pain quantitation of regional myocardial Tl-201 activity was performed by serial scintigraphic images after treadmill exercise. Criteria for an abnormal thallium scintigram included: (a) greater than or equal to 25% persistent reduction in Tl-201 uptake in anterolateral, anteroseptal, posterolateral, and inferoapical segments, or greater than or equal to 35% reduction in the inferior segment; (b) an initial defect with delayed redistribution; and (c) abnormal Tl-201 washout. Of 110 patients with significant coronary artery disease (CAD), 100 had abnormal Tl-201 scintigrams, while 27 of 30 patients with angiographically normal coronary arteries had normal scintigrams; 91% sensitivity, 90% specificity, and 97% predictive accuracy. Sensitivity and specificity were not significantly different when the 95 patients with diagnostic (greater than or equal to 85% maximum heart rate) and 45 with inconclusive (less than or equal to 85% maximum HR) Ex tests were compared. Comparison of qualitative and quantitative image analyses in a subset of these patients showed that both specificity and multivessel disease prediction were greater when the quantitative approach was used (90 against 73% and 78 against 39%, respectively). Sensitivity for CAD detection was reduced by 10% with visual interpretation alone. Thus, quantitative exercise Tl-201 scintigraphy appears highlymore » sensitive and specific for CAD detection in patients with chest pain.« less

Space/time quantitation of thallium-201 myocardial scintigraphy.

Abstract: A comprehensive method is described for quantitation of the spatial distribution of TI-201 in the myocardium and its changes with time. The method, applied here to 51 patients, uses bilinear interpolative background subtraction to compensate for tissue crosstalk, and circumferential profiles to quantitate the relative radionuclide activity in the myocardium as an angular function with origin at the center of the left-ventricular cavity. In addition, washout circumferential profiles are calculated as percent washout from the stress circumferential profiles. Abnormal thallium distribution or washout is identified by automatic computer comparison of each patient's profiles with the corresponding limits of normal profiles, determined from the pooled profiles of 31 normal patients. In these 31, the computer output was normal in all cases. In 20 patients with angiographically documented coronary artery disease, 19 were determined to be abnormal by this method. This new computerized treatment provides accurate objective assessment of the presence of coronary artery disease.

Indium-111 tropolone, a new high-affinity platelet label: preparation and evaluation of labeling parameters.

Abstract: Platelets were isolated with a new neutral, lipid-soluble metal complex of indium-111 and tropolone. Unlike oxine, which must be dissolved in ethyl alcohol, tropolone is soluble saline. Platelet labeling with In-111 tropolone can be performed in both acid-citrate-dextrose (ACD)-plasma and ACD-saline media within two hours' time. Labeling efficiency has been 80-90% in ACD-saline and 60-70% in the ACD-plasma medium. Optimum concentrations for the labeling of platelets with In-111 tropolone were 5 micrograms/ml in ACD-saline and 10 micrograms/ml in ACD-plasma, using a 15-min incubation at room temperature. A kit formulation for convenient routine preparation of In-111-labeled platelets has been developed. Seven parameters of platelet labeling were studied: concentration of tropolone, citrate, plasma proteins, and calcium ions; also platelet density, temperature, and pH of incubation medium. Their effects on the mechanism of platelet labeling with lipid-soluble tracers are discussed.

Imaging the primate adrenal medulla with [123I] and [131I] meta-iodobenzylguanidine: concise communication.

Abstract: An evaluation of radioiodinated meta-iodobenzylguanidine (m-IBG) as an adrenomedullary imaging agent is reported in 15 rhesus monkeys. Scintiscans of the monkey adrenal medulla have been obtained with (/sup 123/I)- and (m-/sup 131/)IBG at 2 to 6 days after injection. The imaging superiority of m-IBG over its positional isomer, para-iodobenzylguanidine (p-IBG), is documented in both dogs and monkeys. Administration of reserpine, a depletor of catecholamine stores, markedly lowers the (m-/sup 131/I)-IBG content of the dog adrenal medulla, but the adrenergic blocking agents phenoxybenzamine and propanolol have no effect. Subcellular fractionation of the dog's adrenal medullae reveals that m-IBG is sequestered mainly in the chromaffin storage granules. The results of this study suggest that radioiodinated m-IBG, previously reported to image the primate myocardium, also merits evaluation as a clinical radiopharmaceutical for the adrenal medulla.

Detection of Ectopic Gastric Mucosa in Meckel's Diverticulum and in Other Aberrations by Scintigraphy: II. Indications and Methods—A 10-Year Experience

Abstract: Ten years' experience with pertechnetate (Tc-99m) abdominal scintigraphy has shown that the method is specifically indicated for the diagnosis and location of ectopic gastric mucosa in a Meckel's diverticulum, in enteric or gastric duplications and cysts, and in Barrett's esophagus. Careful patient preparation is essential, and sequential gamma camera imaging for 1 hr in the anterior projection is advisable, with complementary lateral, upright, and postvoiding views. Nonspecific accumulations of the tracer within tumours, intestinal obstructions, arteriovenous malformations, and the urinary tract can be recognized with the help of the clinical history and can be investigated by other tests. This approach has raised the accuracy of the method above 90%.

Detection of ectopic gastric mucosa in Meckel's diverticulum and in other aberrations by scintigraphy: I. Pathophysiology and 10-year clinical experience.

Abstract: Ten years of clinical experience with pertechnetate (Tc-99m) scintigraphy has proven its validity for the diagnosis of ectopic gastric mucosa in bleeding Meckel's diverticulum and other congenital anomalies. Careful patient preparation and a standardized technique based on sequential gamma imaging has resulted in an overall sensitivity of 85%. Experience in differentiating ''nonspecific'' accumulations of pertechnetate from true ectopic gastric mucosa had increased the specificity to 95%. When we consider all the studies reported (954) with a surgical or clinical diagnosis, the accuracy of the method is calculated at 98%. When only surgically proven cases are analyzed, the calculated accuracy is 90%. Pertechnetate excretion by the mucoid cells of gastric mucosa is the basis of this test. The effect of drugs and hormones on the test has been studied in animals and in patients. The findings suggest that an improvement can be achieved by the use of cimetidine, pentagastrin, or glucagon.

Utility of three-phase skeletal scintigraphy in suspected osteomyelitis: concise communication

Abstract: Three-phase skeletal scintigraphy, consisting of a radionuclide angiogram, an immediate postinjection "blood-pool" image, and 2--3 hr delayed images, was performed on 98 patients with suspected osteomyelitis. This procedure was evaluated by first interpreting only the delayed images, next the combination of "blood-pool" and delayed images, and finally the three-phase study. There was no change in the sensitivity (12/13 = 0.92) for detecting osteomyelitis, but the false-positive rate for osteomyelitis decreased from 0.25 (21/85) to 0.06 (5/85). In 21 of 64 patients (33%) with abnormal studies, the "blood-pool" image and/or the radionuclide angiogram led to a more accurate scintigraphic diagnosis. In 12 patients (19%) the "blood pool" alone was enough to achieve the correct final diagnosis and was used most often to identify noninfectious skeletal disease. In 9 patients (14%) the radionuclide angiogram was required for an accurate interpretation and was considered essential most often in cases of soft-tissue infection. Both radionuclide angiography and "blood-pool" imaging appear to augment the specificity of skeletal scintigraphy in patients with suspected osteomyelitis.

Cationic Tc-99m complexes as potential myocardial imaging agents.

Abstract: Nineteen cationic Tc-99m complexes, based upon four different ligand series, have been synthesized under ''no carrier added'' conditions and qualitatively evaluated as myocardial imaging agents in a dog model. Of these complexes, the four halogen derivatives of the diars series (diars = o-phenylenebis (dimethylarsine)) successfully concentrate in the myocardium. These Tc-99m diars complexes are shown by thin-layer chromatography to be identical to the Tc-99 analogs that have been fully characterized as trans octahedral complexes of Tc(III) by classical chemical techniques. Tissue distribution studies in rats show a definite difference in the biodistributions of (/sup 99m/Tc(diars)/sub 2/Cl/sub 2/)/sup +/ and (/sup 99m/Tc(diars)/sub 2/Br/sub 2/)/sup +/, despite the similar size, shape, charge, and lipophilicity of these two complexes. A tissue distribution study in resting beagle dogs shows that (/sup 99m/Tc(diars)/sub 2/Br/sub 2/)/sup +/ accumulates in the normal myocardium about half as well as Tl-201 (0.022 compared with 0.038% dose/g).

Indium-111-Labeled Human Platelets: Improved Method, Efficacy, and Evaluation

Abstract: An improved method for labeling human platelets with In-111 oxine is described. The method used modified Tyrode's solution (MTS) as a labeling medium and allowed 86 +- 7% incorporation of In-111 into platelets, which upon stimulation with ADP aggregated 66 +- 15% of control platelets. This compared favorably with the 5% radioactivity uptake in plasma and the 36 and 55% aggregability of platelets labeled in saline and citrated saline, respectively. The influence of parameters affecting the platelet aggregability were examined. The studies revealed that excess of oxine (50 ..mu..g oxine/1.6 x 10/sup 9/ platelets in 1 ml MTS), and centrifugation at greater than 1000 g, reduced platelet aggregability. Excess of oxine also caused a dose-dependent release of In-111 from platelets labeled either in MTS or in plasma, but 4 millimol EDTA did not. Release of In-111 upon aggregation of platelets labeled in either medium was negligible.

A boundary method for attenuation correction in positron computed tomography.

Abstract: A new method for attenuation correction in positron computed tomography (PCT) has been developed, and it can improve the quality of PCT images. The method requires a short transmission scan by the PCT system. Then boundaries between tissues with significantly different attenuation coefficients are determined from the transmission image by edge-finding techniques. Attenuation correction factors(ACF) are then calculated using these boundaries and the average attenuation coefficients within the enclosed regions. The method has been tested on computer-simulated data, on scans of phantoms, and on patient studies, and has been found effective in reducing the random noise in transmission measurements and in providing more accurate ACFs than the method using geometric attenuation correction. As a result, transmission scan times can be shortened, inconvenience to patients is reduced, and PCT images are improved.

Does the corticoadrenal adenoma with "pre-Cushing's syndrome" exist?

Abstract: An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. This pattern suggests that the clinical Cushing's syndrome but enough to suppress partially ACTH and, consequently, visualization of the contralateral gland.

Labeling of preformed liposomes with Ga-67 and Tc-99m by chelation.

Abstract: We have synthesized a long-chain hydrocarbon covalently coupled to diethylene-triaminepenta-acetic acid (stearylamine-DTPA) and have incorporated this compound in liposomes during their preparation. The lipophilic hydrocarbon chain anchors the molecule in the lipid bilayer, exposing the DTPA groups on the surface for chelation. Ethanolic solutions of the lipids are evaporated to dryness under nitrogen in multidose vials; the lipids are suspended in the vial by adding a small volume of distilled water followed by sonication. The liposomes are then labeled by transcomplexation in the case of Ga-67 and by conventional stannous reduction in the case of Tc-99m, by adding the activities directly to the vial. These liposomes bind 95 +/- 5% of Ga-67 and Tc-99m activity, as determined by paper chromatograph assay, eliminating the need for a purification step. The labeled liposomes release about 5% of their Ga-67 activity, and about 30% of their Tc-99m activity after 2 hr of incubation in 50% human plasma at 37 degrees C. Activity released from liposomes labeled with Ga-67 or Tc-99m oxine is much greater under the same conditions. In normal mice the labeled liposomes show biodistributions that are comparable with that obtained with liposomes labeled by conventional techniques.

The significance of 1-131 scan dose in patients with thyroid cancer: determination of ablation: concise communication.

Abstract: Twenty-four patients with differentiated thyroid cancer were studied with diagnostic I-131 neck chest scans after having undergone bilateral subtotal thyroidectomy and initial I-131 therapy with either 30- or 100-mCi doses. With an endogenous stimulation protocol, follow-up studies were performed with neck and chest scans using 2 and 10 mCi I-131. A 400% increase in sensitivity was found with a 10-mCi dose relative to a 2-mCi dose. Comparison with therapeutic doses of 30 and 100 mCi resulted in further increases in the detection of residual iodine-avid tissue. We conclude that a 2-mCi or lower dose of I-131 is inadequate in evaluating residual iodine-avid tissue visually in patients with thyroid cancer. The study does not answer the critical question of whether it is necessary to treat a patient presenting a negative 2-mCi but a positive 10-mCi scan. It may be appropriate to define ablation visually as well as clinically, with further studies directed toward determining a treatment rationale in this patient population.

Remote, Semiautomated Production of F-18-Labeled 2-Deoxy-2-Fluoro-d-Glucose

Abstract: A routine production system for 2-deoxy-2-(/sup 18/F)fluoro-D-glucose (2-/sup 18/FDG) for medical use is presented. The method involves the preparation of F-18-labeled F/sub 2/ by the /sup 20/Ne(d,..cap alpha..)/sup 18/F reaction, subsequent fluorination of 3,4,6-tri-0-acetyl-D-glucal, purification, and hydrolysis of the appropriate diastereoisomer to obtain 2-/sup 18/FDG. These operations are performed using a completely remote, semiautomatic system. There have been no failures in more than 220 consecutive production runs. Currently, two preparations per day of 15 to 25 mCi of 2-/sup 18/FDG are routinely performed, with a radiochemical purity, measured by TLC, in excess of 95% and with less than 1 mR radiation exposure to the chemist. Reaction conditions, operational variables, and systems are described in detail.

Lactoferrin: Its Role as a Ga-67-Binding Protein in Polymorphonuclear Leukocytes

Abstract: Gallium-67 bound to lactoferrin - an iron-binding protein found in high concentration in polymorphonuclear leukocytes - has been isolated from PMNs that have previously been incubated with Ga-67 citrate. Although the cell-labeling efficiency was highly variable (0.026-10%), much of the activity that did bind to the PMNs (74.8 +- 10%) was recovered in the supernatant after sonication and centrifugation. About half (approx. 47%) of the PMN-bound activity was retained after dialysis and was presumably bound to macromolecules in the supernatant. When this retained activity was placed on a column containing immobilized antilactoferrin antibody, almost three quarters of the activity was bound to the column. This bound activity was (36 +- 17%) of the total activity absorbed by the PMN. The addition to the antilactoferrin column of a known antigen-antibody-dissociating agent caused the dissolution of the complex. No significant activity was bound to a control column. The findings indicate that lactoferrin is a major Ga-67-binding protein present in PMNs and suggest that it may play a major role in Ga-67 localization in an abscess. These results support the contention that molecules binding ferric iron have an important effect on Ga-67 distribution in vivo.

Cerebral blood flow using PET measurements of fluoromethane kinetics.

Abstract: The development of a tomographic method of measuring regional cerebral blood flow, based on positron-emission tomographic determination of the regional cerebral kinetics of fluoromethane (F-18) (methyl fluoride) is reported. The high Ostwald solubility of fluoromethane has allowed development of a blood-flow method that takes advantage of the decades of previous blood-flow investigations with inert tracers, yet provides tomographic determinations at a spatial resolution approaching those of methods based on regional tissue deposition of radioactivity. Refinements of the method are proceeding and with a variety of clinical and research applications.

Se-75-labeled Bile Acid Analogs, New Radiopharmaceuticals for Investigating the Enterohepatic Circulation

Abstract: Four selenium-labeled free bile acids and four selenium-labeled conjugated bile acids, labeled with Se-75 at the C-19, C-22, C-23, or C-24 position, have been synthesized and their absorption and excretion compared with that of (24-14C)cholic acid, following both oral and intravenous administration. All but one of the compounds is absorbed and excreted in bile to a significant extent. One compound, SeHCAT, has been selected for particular study. It is quantitatively absorbed from the gut at the same rate as cholic acid, and both are excreted into the bile at the same rate. It remains almost entirely confined to the enterohepatic circulation (the gut, liver, and biliary tree) and excretion is exclusively fecal. Whole-body retention, measured for 41 days, and tissue distributions suggest that the absorbed radiation dose would be small compared with that in many established tests. Such a compound offers the possibility of a simple, novel, and aesthetically acceptable method of investigating small-bowel disease. It therefore merits further investigation.

A Shielded Synthesis System for Production of 2-Deoxy-2-[18F]Fluoro-d-Glucose

Abstract: A remotely operated, shielded synthesis system for the production of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) for clinical studies has been developed. Using this system, 25 mCi of 18FDG are produced a the end of a 60-min synthesis from approximately 300 mCi of F-18 (total F-18 recovered from the target at the end of bombardment). The fractional distribution of F-18 among various components of the synthesis system has been measured. This yield of 18FDG (25 mCi) is ample for two consecutive human studies in house or for shipment to collaborating institutions within a 3-hr (door to door) radius.

Chemical and biological studies of Tc-99m N,N'-bis(mercaptoacetamido)-ethylenediamine: a potential replacement for I-131 iodohippurate.

Abstract: The tetradentate chelating agent N,N'-bis(benzoylmercaptoacetamido)ethylenediamine was synthesized for evaluation as a potential technetium-99m renal-function radiopharmaceutical. Complexes were prepared using different reducing agents and analyzed by high-performance liquid chromatography. Biological studies were performed in mice, rats, and rabbits and indicated that the new agent is cleared by the kidneys significantly faster than Tc-99m DTPA (p less than 0.01) and slightly slower than I-131 o-iodohippuric acid (p greater than 0.05). There was no evidence of significant renal retention. Renal excretion in all species studied was 70--75% of the injected dose in 30 min; biliary excretion in rats was 7% in animals with normal renal function and 18% in 90 min in the absence of renal function. We conclude that limited clinical trials are warranted.

16 alpha-[77Br]bromoestradiol-17 beta: a high specific-activity, gamma-emitting tracer with uptake in rat uterus and uterus and induced mammary tumors.

Abstract: 16 alpha-[77Br]Bromoestradiol-17 beta (Compound 1) has been synthesized by radiobromination of estrone enoldiacetate. Tissue uptake studies performed 1 hr after administration of Compound 1 to immature or mature female rats showed uterus-to-blood ratios of 13, with nontarget issue-to-blood ratios ranging from 0.6 to 2. Co-administration of unlabelled estradiol caused a selective depression in the uterine uptake with no effect on nontarget tissue uptake. In adult animals bearing adenocarcinomas induced by DMBA (7,12-dimethylbenz(a)anthracene), tumor-to-blood ratios of 6.3 were obtained, this uptake also being depressed in animals treated with unlabeled estradiol. The studies demonstrate that Compound 1 has suitable binding properties and sufficiently high specific activity so that its uptake in estrogen target tissues in vivo is mediated primarily by the estrogen receptor. Furthermore, they suggest that this compound may be suitable for imaging human breast tumors that contain estrogen receptors.

Positron imaging feasibility studies. II: Characteristics of 2-deoxyglucose uptake in rodent and canine neoplasms: concise communication.

Abstract: Uptake of [3H]2-deoxyglucose was studied in BALB/c mice with EMT-6 sarco ma, in Buffalo rats with Morris 7777 hepatoma, and in eight dogs with spontaneous neoplasms: five osteosarcomas and three diffuse lymphomas. High tumor-to-tissue ratios were observed for all tumor types studied. In rodents, peak levels of uptake occurred between 30 min and 1 hr, with a slow loss from the tumor of about 10% per hour thereafter. In dogs there was considerable variability in uptake, both be tween Individuals and at different tumor sites within an individual. Necrotic tumor did not take up the radiotracer. Absolute uptakes, when normalized for body weight, were similar for spontaneous and transplanted neoplasms. These studies provide additional support for the concept that positron emission tomography can be used to obtain functional images of important metabolic pro cesses of tumors, including glycolysis.

Variable angle slant hole collimator

Abstract: A variable angle radiation collimator particularly for use in gamma-photon medical diagnostic systems in a gamma-photon camera system for radiological examination of human subjects. The collimator provides collimation of gamma-photon radiation along a single beam direction which may be varied along two axes to adjust exposure angle or to provide a scanning capability. The collimator is a stack of substantially identical radiation-opaque plates, each of which are apertured with a similar array of openings. The combined effect of the stacked aperture plates is to transmit radiation in a predetermined orientation. The collimated angle of the radiation thus generated is controlled by the coincidence of the array of openings. The stack is retained by a mechanism which permits adjustment of the collimation angle, and the plates are fabricated to provide ease of shear motion during such adjustment. In addition, the tradeoff between the resolution and intensity of radiation transmitted may be easily varied by adjusting stack thickness.

Localization of Tc-99m MDP in Epiphyseal Growth Plates of Rats

Abstract: The distribution and localization of Tc-99m methylene diphosphonate (Tc-MDP) in the epiphyseal growth plates of the rat were elucidated by contact and microautoradiography. The uptake of the tracer was found to be especially high in the calcified cartilage bars at the end of the vascular loops. In addition to areas of mineralization, increased uptake was found in the Howship's lacunae on the resorbing surfaces. This labeling corresponded with the fluorescence of tetracycline, which labeled both forming and resorbing surfaces, when given with short labeling interval. Distribution of Tc-MDP did not coincide with new production of collagen, as judged by H-3 proline labeling; nor was the uptake localized within cells with high alkaline phosphatase activity. The affinity of the tracer for the mineral phase was confirmed by decalcification of in vivo labeled sections with EDTA, whic showed loss of radioactivity in contrast to sections incubated in water. By chromatography the activity in the decalcification medium could not be distinguished from that of Tc-MDP.

Real-time scintillation probe measurement of left ventricular function.

Abstract: A nonimaging, ECG-gated scintillation-probe system is described that permits real-time quantification, at high temporal resolution, of the time variation of left ventricular (LV) volume over a complete, average cardiac cycle. Linearity between counting rate and volume, probe positioning, and background correction were investigated for both cylindrically collimated (CC) and parallel-hole-collimated (PC) detectors. In 53 patient studies, results obtained with these probes were compared with results obtained from an ECG-gated gamma camera system (CS) with high temporal resolution. Time-activity curves obtained by all three devices were essentially identical in shape (for CC against CS, r = 0.93; for PC against CS, r = 0.98) and in intracycle timing. Left-ventricular ejection fractions obtained with the probes showed workable agreement with the camera: for CC against CS, r = 0.85 (N = 31); for PC against CS, r = 0.90 (N = 21). When LV background is removed as a source of error, the correlation between (PC) probe and camera is improved (r = 0.95, N = 21). This suggests that the portable probe system be used in circumstances where exact knowledge of LV background is minimally important--e.g., continuous bedside monitoring of changes in LV function.

Tc-99m DMSA Renal Uptake: Influence of Biochemical and Physiologic Factors

Abstract: Thirty-eight female Sprague-Dawley rats were studied to determine the effects of (a) tubular blockade and (b) commonly encountered changes in hydration and acid-base balance, on the urinary excretion and renal localization of Tc-99m dimercaptosuccinic acid (DMSA). Ten additional rats were studied to quantitate the in vivo protein binding of Tc-99m DMSA, and a final group of 12 animals was used to quantitate DMSA distribution in animals with diminished functional renal mass. Both osmotic diuresis and dehydration by water deprivation for 24 hr resulted in a plasma clearance of DMSA slower than in control animals. Acid-base imbalances significantly affected the renal accumulation of DMSA, and acidosis was associated with markedly increased background due to increased liver accumulation. The protein-bound portion of Tc-99m DMSA in the plasma was high, reaching 89% within the first 5 min, and rising very slightly (n.s.) ith time. The unbound portion of DMSA had a plasma clearance slightly higher than the GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR. Ablation of large amounts of renal tissue, resulting in significant decreases in GFR, did not significantly affect the renal localization of DMSA in the intact portions of the kidneys. These data demonstrate that commonly encountered changes in acid-base balance and hydration will significantly alter the biologic distribution of Tc-99m DMSA. These factors should be controlled when carrying out clinical studies.

Decreased accumulation of isopropyl-iodoamphetamine (I-123) in brain tumors

Abstract: Four out of four patients with brain tumors were observed to have impaired N-isopropyl-p-(/sup 123/I)iodoamphetamine (IAMPH) accumulation by the lesions even though brain scans with technetium-99m diethylenetriamine pentaccetic acid were normal in two. IAMPH may be a more sensitive means of detecting regional cerebral disease than tracers primarily sensitive to blood-flow abnormalities or impairment of the blood-brain barrier.

Technetium Radiopharmaceuticals: Chemical Characterization and Tissue Distribution of Tc-Glucoheptonate Using Tc-99m and Carrier Tc-99

Abstract: The chemical structure of the kidney- and brain-imaging agent Tc-99m glucoheptonate has been established using the Tc-99 isotope. In a comparative study between Tc-99 and Tc-99m glucoheptonates, chromatographic, electrophoretic, and tissue distribution studies showed identical compounds in 0.9% NaCl. Optimal conditions for the formation of the Tc-99 glucoheptonate complex were investigated by uv and visible spectroscopy. The oxidation state of Tc-99 in the compound is V, measured by Sn2+ titration. The complex contains a Tc . O core and two glucoheptonate ligands (oxobis(glucoheptonato)technetate(V) anion (net charge: -1) in aqueous solution). NMR studies demonstrated two five-membered glucoheptonate rings, bidentate bound to Tc by the oxygens of the end carboxyl group and the adjacent hydroxyl group. The compound is stabilized by interaction between Tc-99 and one of the hydroxyloxygens of glucoheptonate at the vacant coordination site trans to the Tc . O core. Experiments with the reducing agent NaBH4 demonstrated the absence of Sn (II or IV) in the complex and a biological behavior independent of the reducing agent used.