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Biomedical subjects

J L Lear

Publications and source records attributed to J L Lear.

At least 37 records · Page 2Linked to original sources
PubMed1990

Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen.

To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h, respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted.

Antibodies, Monoclonal↗
PubMed1990

Evaluation of radiolabeled acetate and fluoroacetate as potential tracers of cerebral oxidative metabolism.

We investigated the potential use of radiolabeled acetate (ACE) and fluoroacetate (FACE) as tracers of cerebral oxidative (Krebs cycle) metabolism. The rates of cerebral accumulation of 14C-labeled FACE and ACE were compared with glucose metabolic rates measured simultaneously with 18F-fluorodeoxyglucose (FDG) in awake rats using dual-tracer quantitative digital autoradiography. Both FACE and ACE crossed the blood-brain barrier at approximately the same rate as glucose. Metabolism of FACE by the brain, however, was extremely slow; metabolites were practically undetectable above background precursor levels through 60 min. Metabolic uptake of ACE by the brain was significant by 10 min; its rate of accumulation averaged approximately 70-80% of the glucose rate. While the metabolic images of ACE were similar to those of FDG, variations in the uptake patterns of FDG and ACE occurred in some structures, perhaps related to regional variations in glucose versus oxygen metabolism.

Acetates↗
PubMed1990

Mapping regional cerebral vascular transit time by simultaneous determination of local cerebral blood flow and local cerebral blood volume.

We developed a method for autoradiographic mapping of regional cerebral transit time (CTT) by simultaneously measuring local cerebral blood flow (LCBF) and local cerebral blood volume (LCBV). Previously described single-tracer techniques for determination of LCBF and LCBV were modified for dual-tracer, 99mTc and 14C, autoradiography and used to create digital images of LCBF and LCBV from the same brain sections in a series of normal rats. The images were aligned and ratio images (LCBV/LCBF) were then generated which reflected CTT. Regional cerebral transit time was found to vary significantly through-out the brain in a pattern only partially related to that of blood flow. Such CTT heterogeneity could cause errors in implementation of kinetic models which assume uniform or monovariant distributions of vascular transit time.

Animals↗
PubMed1990

Ultra-high performance, solid-state, autoradiographic image digitization and analysis system.

We developed a Macintosh II-based, charge-coupled device (CCD), image digitization and analysis system for high-speed, high-resolution quantification of autoradiographic image data. A linear CCD array with 3,500 elements was attached to a precision drive assembly and mounted behind a high-uniformity lens. The drive assembly was used to sweep the array perpendicularly to its axis so that an entire 20 x 25-cm autoradiographic image-containing film could be digitized into 256 gray levels at 50-microns resolution in less than 30 sec. The scanner was interfaced to a Macintosh II computer through a specially constructed NuBus circuit board and software was developed for autoradiographic data analysis. The system was evaluated by scanning individual films multiple times, then measuring the variability of the digital data between the different scans. Image data were found to be virtually noise free. The coefficient of variation averaged less than 1%, a value significantly exceeding the accuracy of both high-speed, low-resolution, video camera (VC) systems and low-speed, high-resolution, rotating drum densitometers (RDD). Thus, the CCD scanner-Macintosh computer analysis system offers the advantage over VC systems of the ability to digitize entire films containing many autoradiograms, but with much greater speed and accuracy than achievable with RDD scanners.

Animals↗
PubMed1990

Gamma camera image acquisition, display, and processing with the personal microcomputer.

The authors evaluated the potential of a microcomputer for direct acquisition, display, and processing of gamma camera images. Boards for analog-to-digital conversion and image zooming were designed, constructed, and interfaced to the Macintosh II (Apple Computer, Cupertino, Calif). Software was written for processing of single, gated, and time series images. The system was connected to gamma cameras, and its performance was compared with that of dedicated nuclear medicine computers. Data could be acquired from gamma cameras at rates exceeding 200,000 counts per second, with spatial resolution exceeding intrinsic camera resolution. Clinical analysis could be rapidly performed. This system performed better than most dedicated nuclear medicine computers with respect to speed of data acquisition and spatial resolution of images while maintaining full compatibility with the standard image display, hard-copy, and networking formats. It could replace such dedicated systems in the near future as software is refined.

Gamma Cameras↗
PubMed1990

Quantification of patterns of regional cardiac metabolism.

To quantitatively map and compare patterns of regional cardiac metabolism with greater spatial resolution than is possible with positron emission tomography (PET), the authors developed autoradiographic techniques for use with combinations of radiolabeled fluorodeoxyglucose (FDG), glucose (GLU), and acetate (ACE) and applied the techniques to normal rats. Kinetic models were developed to compare GLU-based oxidative glucose metabolism with FDG-based total glucose metabolism (oxidative plus anaerobic) and to compare ACE-based overall oxidative metabolism with FDG-based total glucose metabolism. GLU-based metabolism generally paralleled FDG-based metabolism, but divergence occurred in certain structures such as the papillary muscles, where FDG-based metabolism was much greater. ACE-based metabolism also generally paralleled FDG-based metabolism, but again, the papillary muscles had relatively greater FDG-based metabolism. These discrepancies between FDG-based metabolism and GLU- or ACE-based metabolism suggest the presence of high levels of anaerobic glycolysis. Thus, the study indicates that anaerobic glycolysis, in addition to occurring in ischemic or "stunned" myocardium (as has been shown in recent PET studies), occurs normally in specific cardiac regions, despite the presence of abundant oxygen.

Acetates↗
PubMed1989

Regional comparison of the lumped constants of deoxyglucose and fluorodeoxyglucose.

We determined the regional relationships of the lumped constants for deoxyglucose (DG) and fluorodeoxyglucose (FDG). Awake male rats were given simultaneous intravenous injections of [14C]DG and [18F]FDG, and sacrificed after 45 min. The brains were removed and small pieces of cortical tissue were sampled by dissection. The remainder of the brains were frozen and sliced into 20-microns-thick sections that were placed on coverslips and dried on a hot plate. Two sets of brain autoradiograms were prepared from the brain sections, one representing predominantly [14C] and the other [18F]. The autoradiograms were digitized, and after correcting for cross-contamination, tracer-concentration images of the DG and FDG were generated. Based on relative tracer concentrations in the tissue samples, the lumped constant of FDG was found to be 1.25 times that of DG, or 0.6. Using this value, images of glucose metabolism for the DG and FDG were generated from the tracer concentration images and compared. No significant regional differences were found, indicating that the relationship between the lumped constant of DG and that of FDG was stable throughout the normal brain.

Animals↗
PubMed1989

Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose.

We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered [18F]fluorodeoxyglucose (FDG) and [14C]-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the 14C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the 14C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum.

Animals↗
PubMed1989

Ultra-high-speed teleradiology with ISDN technology.

A solid-state, personal computer-based, image digitization and transmission system was developed that uses integrated services digital network (ISDN), a technology under development for ultra-high-speed data transmission over normal phone lines. Thousands of images have been transmitted to a site more than 15 miles away, with data rates exceeding 56,000 bits or 7,000 bytes (1 byte = 8 bits) per second with nearly perfect accuracy. Present modification of the system hardware and software should increase the data rate to 128,000 bits, or 16,000 bytes, per second. With this rate of transmission, remote radiologic image transmission should become a practical, routinely available diagnostic tool.

Computer Communication Networks↗
PubMed1989

Two-compartment, two-sample technique for accurate estimation of effective renal plasma flow: theoretical development and comparison with other methods.

Discordance between effective renal plasma flow (ERPF) measurements from radionuclide techniques that use single versus multiple plasma samples was investigated. In particular, the authors determined whether effects of variations in distribution volume (Vd) of iodine-131 iodohippurate on measurement of ERPF could be ignored, an assumption implicit in the single-sample technique. The influence of Vd on ERPF was found to be significant, a factor indicating an important and previously unappreciated source of error in the single-sample technique. Therefore, a new two-compartment, two-plasma-sample technique was developed on the basis of the observations that while variations in Vd occur from patient to patient, the relationship between intravascular and extravascular components of Vd and the rate of iodohippurate exchange between the components are stable throughout a wide range of physiologic and pathologic conditions. The new technique was applied in a series of 30 studies in 19 patients. Results were compared with those achieved with the reference, single-sample, and slope-intercept techniques. The new two-compartment, two-sample technique yielded estimates of ERPF that more closely agreed with the reference multiple-sample method than either the single-sample or slope-intercept techniques.

Humans↗
PubMed1988

Reverse and pseudo redistribution of thallium-201 in healed myocardial infarction and normal and negative thallium-201 washout in ischemia due to background oversubtraction.

While the interpolative background subtraction used in quantitative planar thallium scanning can significantly overestimate the background overlying the heart, the effects of background oversubtraction on quantitative analysis have not been well defined. A mathematical model that relates myocardial washout determined using interpolative background subtraction to true myocardial washout is presented. The model was validated using phantoms and applied to myocardial and pulmonary thallium kinetic data in 100 patients, 85 with and 15 without coronary artery disease. The model showed that when using interpolative background subtraction, measured washout equals true washout in normally perfused myocardium; however, depending on the relation between myocardial and pulmonary thallium clearance, myocardial washout in ischemic regions and areas of infarction can be substantially over- or underestimated. Based on generally accepted quantitative criteria, this incorrect washout determination can at times lead to misdiagnosis of infarction as ischemia and ischemia as normally perfused tissue. It can also cause both "reverse redistribution" and "pseudo redistribution" of thallium in myocardial infarction in the absence of a physiologic basis.

Coronary Disease↗
PubMed1988

Initial cerebral HM-PAO distribution compared to LCBF: use of a model which considers cerebral HM-PAO trapping kinetics.

The cerebral uptake of [99mTc]-d,l-hexamethylpropyleneamine oxime complex (HM-PAO) was compared to LCBF determined simultaneously with [14C]iodoantipyrine (IAP) using double radionuclide quantitative digital autoradiography. Awake male rats were given intravenous injections of a mixture of 50 microCi IAP and 15 mCi of HM-PAO and killed 20 s after tracer activity had first reached the brain. Two separate autoradiograms were produced from each 20 microns brain section. The autoradiograms were digitized, corrected for cross-contamination, and then converted into images of individual tracer concentration. The diffusible tracer model was used to convert the IAP concentration images into LCBF images. Regional HM-PAO concentration was found not to be linearly related to LCBF as determined with the IAP, and therefore a simple microsphere type model was inadequate in relating HM-PAO uptake to LCBF. A better HM-PAO uptake--LCBF correlation was obtained when the HM-PAO arterial input function was corrected for very rapidly produced, non-cerebrally extracted, metabolites and a kinetic model was used that considered the rate of intracerebral metabolism of HM-PAO to a retained metabolite. Even using this model, however, some differences between HM-PAO uptake and LCBF occurred in certain brain regions. Because these differences were small and the HM-PAO uptake pattern has been shown to be constant for many minutes, HM-PAO can probably be used to estimate LCBF in patients with single positron emission computed tomography (SPECT) imaging.

Animals↗
PubMed1988

Comparison of cerebral glucose metabolic rates measured with fluorodeoxyglucose and glucose labeled in the 1, 2, 3-4, and 6 positions using double label quantitative digital autoradiography.

We compared local cerebral glucose metabolic rates (LCMRglu) that were determined with [18F]fluorodeoxyglucose (FDG) and [14C]glucose labeled in the 1, 2, 3-4, and 6 positions. Double label digital autoradiography was used with published kinetic models to determine LCMRglu for FDG and glucose in the same animals. Glucose showed metabolic rate dependent underestimation of LCMRglu compared to FDG, which worsened with increasing experimental times. The least underestimation occurred with glucose labeled in the 6 position at 6 min, reaching 10% in areas of high metabolism. Labeling in the 1 position, the 2 position and the 3-4 position caused progressively worse underestimation at all times. In addition, some structures showed differences not directly related to metabolic rate, indicating regional variations in relationships between individual kinetic constants of FDG and glucose.

Animals↗
PubMed1988

Quantitative local cerebral blood flow measurements with technetium-99m HM-PAO: evaluation using multiple radionuclide digital quantitative autoradiography.

We investigated d,1 [99mTc]hexamethylpropyleneamine oxime complex (HM-PAO) as a tracer for quantitative measurement of local cerebral blood flow (LCBF) in a series of awake male rats. LCBF measurements with HM-PAO were compared to those of two other tracers, [14C] iodoantipyrine (IAP) and [201Tl]diethyldithiocarbamate (DDC), using quantitative double and triple tracer digital autoradiography. LCBF values with HM-PAO averaged 64% those of IAP and were generally linearly related. Detailed analysis suggested that the underestimation of LCBF by HM-PAO was related to blood constituent binding and/or rapid conversion to a noncerebrophilic compound, as well as noninstantaneous cerebral trapping, rather than to diffusion limitation.

Animals↗
PubMed1988

Quantitative measurement of renal perfusion following transplant surgery.

We developed an easily implemented clinical procedure for quantitative perfusion measurements in transplanted kidneys using intravenously administered [99mTc]DTPA and the tracer fractionation technique. F = Ak(T)/0 integral of T [Aa(t)/Va] dt, where F = renal blood flow, Ak(T) = DTPA activity in kidney at time = T, Va = ultrasonographically measured femoral artery segment volume, T = time postinjection of F determination, and Aa(t) = time course of DTPA activity in femoral artery segment. The technique was applied to a group of 80 studies in 35 patients in whom an independent clinical determination of transplant function was available. Blood flow (units of ml/min) measured 439 +/- 83 in normally functioning transplants, 248 +/- 63 in transplants with acute tubular necrosis, 128 +/- 62 in transplants with rejection, and 284 +/- 97 in transplants with cyclosporine toxicity. These preliminary results indicate potential usefulness of this method in the evaluation of renal function following transplant surgery.

Femoral Artery↗