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Biomedical subjects

C D Russell

Publications and source records attributed to C D Russell.

At least 55 records · Page 3Linked to original sources

Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody.

Pharmacokinetics, immunogenicity, and biodistribution of a 131I-labeled mouse/human chimeric monoclonal antibody (C-17-1A) was studied in six metastatic colon cancer patients. Pharmacokinetics obtained from serum radioactivity or chimera concentration were identical after 5 mCi of 131I-C-17-1A with mean alpha half-lives of 17.6 +/- 2.3 and 19.7 +/- 2.9 and mean beta half-lives of 100.9 +/- 16.1 and 106.4 +/- 14.1 hr, respectively. HPLC analysis documented the monomeric chimeric 17-1A without evidence of immune complexes or free 131I. None of the patients developed antibody after 131I-chimeric 17-1A exposure. Radiolocalization occurred in known areas of disease greater than 4 cm in all patients. The half-life of total-body radioactivity was 58 +/- 7 hr by whole-body counts and 64 +/- 13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1.03 and 0.76-1.05 rad/mCi, respectively. These studies confirm the prolonged circulation and reduced immunogenicity of chimeric 17-1A versus murine 17-1A. Marrow radiation exposure using antibodies with prolonged circulation is a critical factor in planning for radioimmunotherapeutic applications.

Adenocarcinoma↗

Measurement of renal parenchymal transit time of 99mTc-MAG3 using factor analysis.

Renal parenchymal transit time of the recently introduced radiopharmaceutical 99mTc-MAG3 (mercaptoacetylglycylglycinel) was measured in 37 kidneys, using factor analysis to separate parenchymal activity from that in the collecting system. A new factor algorithm was employed, based on prior interpolative background subtraction and use of the fact that the initial slope of the collecting system factor time-activity curve must be zero. The only operator intervention required was selection of a rectangular region enclosing the kidney (by identifying two points at opposite corners). Transit time was calculated from the factor time-activity curves both by deconvolution of the parenchymal factor curve and also by measuring the appearance time for collecting system activity from the collecting system factor curve. There was substantial agreement between the two methods. Factor analysis led to a narrower range of normal values than a conventional cortical region-of-interest method, presumably by decreasing crosstalk from the collecting system. In preliminary trials, the parenchymal transit time did not well separate four obstructed from seventeen unobstructed kidneys, but it successfully (p less than 0.05) separated six transplanted kidneys with acute rejection or acute tubular necrosis from 10 normal transplants.

Algorithms↗

Estimation of ERPF in adults from plasma clearance of 131I-hippuran using a single injection and one or two blood samples.

The plasma clearance of [131I]o-iodohippurate, which is an estimate of effective renal plasma flow, can be measured from one or two blood samples drawn after an i.v. bolus of tracer. The most widely used method is based on a single sample. Here, it is shown that the error (relative to a complete curve of six or more blood samples) can be halved by using two samples rather than one. Since the one-sample method is satisfactory for most clinical purposes, the two-sample method is recommended only when special accuracy is needed.

Blood Specimen Collection↗

The kidney: imaging with Tc-99m mercaptoacetyltriglycine, a technetium-labeled analog of iodohippurate.

A new renal imaging agent, technetium-99m mercaptoacetyltriglycine (MAG3, mertiatide), is currently undergoing clinical trials. Like iodine-131 orthoiodohippurate (OIH)--and unlike all other available agents--it is avidly secreted by the renal tubules. Fifty patients underwent simultaneous renal imaging studies with I-131 OIH and Tc-99m MAG3. The superior physical properties of the Tc-99m label led to better image quality in all cases, largely due to count rates that were 50-fold better. In two patients, lesions were seen with MAG3 that were not visible with OIH. The biological properties of the two agents were found to be so similar that conventional diagnostic criteria for I-131 OIH could be used for Tc-99m MAG3 with only minor modifications.

Humans↗

Estimation of technetium-99m-MAG3 plasma clearance in adults from one or two blood samples.

Technetium-99m mercaptoacetyltriglycine (MAG3) clearance is strongly correlated with effective renal plasma flow and can be used directly as a measure of renal function. For these reasons, formulas were developed for estimation of [99mTc]MAG3 clearance based on one or two plasma samples. A two-exponential model provided an excellent fit for 8-point plasma clearance curves obtained from 35 patients having a wide range of renal function. The 8-point [99mTc]MAG3 clearance could be estimated from a single point at 43 min with an error of 19 ml/min (residual s.d.) or from two samples at 12 and 94 min with an error of 7 ml/min. The relative errors with MAG3 are thus comparable to those reported for similar techniques used with [131I]orthoiodohippurate, [99mTc]diethylenetriaminepentraacetic acid and [51Cr]ethylenediaminetetraacetic acid.

Adult↗

Measurement of renal function with radionuclides.

For the nuclear physician who wants to measure renal function, the biggest problem may be having to choose among the dozens of methods that have been proposed. An overview will be presented here. The final selection must depend upon the needs of each clinic as well as its technical and financial resources. Except at very low levels of renal function, almost any of these methods can be more reliable than creatinine clearance.

Humans↗

Radionuclide evaluation of renal transplants.

In this review article, the following topics are treated: the radiopharmaceuticals 99mTc-diethylenetriaminepentaacetic acid (DTPA), 131I-orthoiodohippurate (OIH), 99mTc-mercaptoacetyltriglycine (MAG3), 67Ga-citrate, radioiodinated fibrinogen, 99mTc-sulfur colloid, 111In-labelled white cells and platelets; gamma camera methods based on images, on first pass and on tubular transit; blood clearance methods; and the diagnosis of surgical complications, acute rejection (AR), acute tubular necrosis (ATN), chronic rejection (CR), and cyclosporine-A (CYA) toxicity.

Graft Rejection↗

Clinical use of a standard kit-preparation of radiolabeled monoclonal antibody 96.5 in the diagnostic imaging of metastatic melanoma.

We studied the efficiency of a standard-kit preparation using 1 mg 111In-labeled 96.5 monoclonal antibody in combination with 19 mg of unlabeled antibody in the diagnostic imaging of 27 patients with documented metastatic melanoma. Twenty-three of 26 patients (88%) demonstrated immunoscintigraphic localization of tumor. Of 104 metastatic sites previously documented by conventional studies, 62 (60%) were identified by immunoscintigraphy. A total of 77 sites demonstrated localization of radiolabeled antibody. Fifty-four (70%) corresponded to known sites of disease; eight sites (10%) were "discovered" by immunoscintigraphy and subsequently confirmed by conventional studies; 15 imaged sites (20%) could not be confirmed by conventional studies. Size and location of metastasis appear to be important features that influence imaging efficiency. Tumor size (greater than or equal to 2 cm v less than 2 cm) appears to be the statistical dominant determinant. The feasibility and potential clinical use of radioimmune imaging of tumors is discussed.

Adult↗

Comparison of technetium-99m MAG3 with iodine-131 hippuran by a simultaneous dual channel technique.

Technetium-99m MAG3, a technetium-labeled analog of hippuran, was compared with [131I] hippuran using a simultaneous dual isotope study in 20 patients. The plasma clearance for MAG3 was lower than that of hippuran, but its plasma concentration was higher, resulting in similar rates of excretion and similar renal time-activity curves. Apart from better statistics with the technetium-labeled agent, there were no clinically significant differences in this group of patients.

Adult↗

Abnormal captopril renogram with a technetium-99m-labeled hippuran analog.

A case of renovascular hypertension is presented in which the [131I]hippuran renogram was initially normal, but became strikingly abnormal upon administration of the angiotensin converting enzyme (ACE) inhibitor captopril. The patient presented with fibromuscular dysplasia of the renal arteries, which was shown by hippuran renography to be functionally significant on the right side. She became normotensive after angioplasty of the right renal artery. Hypertension recurred a year later, at which time the renogram was normal without captopril, but showed functionally significant left renal artery stenosis with captopril challenge. Both the conventional agent, [131I]hippuran, and an experimental new 99mTc-labeled hippuran analog, [99mTc]MAG3, were used. Angiography confirmed progression of disease on the left side, which was successfully treated by angioplasty. Functionally significant unilateral renal artery stenosis was thus demonstrated first on the right side and then, 1 yr later, on the left side, using hippuran and [99mTc]MAG3. Anatomic progression of disease was documented by angiography.

Adult↗

Quantitation of renal function with technetium-99m MAG3.

The technetium-labeled hippuran analog [99mTc]MAG3 was compared with [131I]hippuran in 50 patients using a quantitative renal function protocol that includes: (a) estimation of effective renal plasma flow by a single-injection, single-sample plasma clearance method, (b) determination of relative function of right and left kidney from the initial count rate over each kidney, and (c) comparison of recovered urine activity with plasma disappearance. This protocol is suitable for routine clinical use, and, in fact, has been used heavily at our clinic for a number of years. By slight modification of the formulas, the results obtained with [99mTc]MAG3 agreed well with those using [131I]hippuran. We conclude that [99mTc]MAG3 can be substituted for [131I]hippuran in the quantitative protocol, with the better image quality and lower radiation dose (in abnormals) of a technetium-labeled agent.

Humans↗

Estimation of extracellular fluid volume from plasma clearance on technetium-99m DTPA by a single-injection, two-sample method.

A simple method is presented for estimating extracellular fluid volume from the plasma clearance of [99mTc])DTPA or [169Yb]DTPA. Two plasma samples are required, at 1 and 3 hr, following a single intravenous injection. (The same plasma samples can be used for measurement of glomerular filtration rate.) Using the complete plasma clearance curve as a reference (eight samples at 10 to 240 min), the error of the two-sample method in 40 patients was 1.5 I for [99mTc]DTPA, 2.1 I for [169Yb]DTPA (residual standard deviation).

Extracellular Space↗

Estimation of glomerular filtration rate using 99mTc-DTPA and the gamma camera.

Two methods of glomerular filtration rate estimation have been evaluated, based on the intravenous administration of 99mTc-DTPA and the measurement of renal time activity curves by means of a computer linked gamma camera. A single 20 min plasma sample was also required. These methods were designed to minimize the component of error arising from decay statistics. One method was based on using a constant fraction of the cardiac activity in lieu of a perirenal region of interest for the background correction, the other was based on deconvolution by a constrained least squares technique. The first method, based on modifying the background correction, led to poor results (residual standard deviation 18.9 ml/min when compared with the plasma clearance method). The second method, based on constrained least squares deconvolution, worked as well as previously reported methods (residual standard deviation 14.5 ml/min) and appears suitable for clinical use.

Glomerular Filtration Rate↗

Quality control of technetium-99m DTPA: correlation of analytic tests with in vivo protein binding in man.

When [99mTc]DTPA is administered, a small fraction of the activity (presumably an impurity) is bound to plasma proteins. This causes an error in the calculation of glomerular filtration rate from plasma clearance. This paper presents two methods of laboratory quality control for measuring the fraction that binds to plasma proteins. One method involves in vitro binding to human serum albumin followed by gel filtration. The other method involves descending paper chromatography on wet pre-equilibrated anion exchange paper. In a series of 80 patients, correlation was demonstrated between laboratory characteristics and actual clinical performance of the [99mTc]DTPA preparation. Both laboratory methods appear suitable for routine quality control.

Blood Proteins↗