PubMed Health⌕ Search

Biomedical subjects

J G McAfee

Publications and source records attributed to J G McAfee.

At least 19 recordsLinked to original sources
PubMed1991

Technetium-99m-labeled proteins for imaging inflammatory foci.

Polyclonal human IgG (IgG), antinuclear antibody (TNT-1), and human serum albumin (HSA), were labeled with 99mTc by a method recently developed in our laboratory, and administered i.v., each to a separate group of five mice, bearing inflammatory foci induced by an i.m. injection of 40 microL turpentine or 5 x 10(8) E. coli and 5 x 10(8) Entercocci. TNT-1 labeled with 125I served as a control and 67Ga-citrate as a "gold standard". At 4 or 24 h post injection, animals were imaged and sacrificed for tissue distribution studies. At 4 h in the turpentine group, the abscess-to-muscle ratios were: 67Ga, 4.8 +/- 2.1, 125I-TNT-1, 4.3 +/- 1; 99mTc-TNT-1, 3.5 +/- 1.8; 99mTc-IgG, 3.9 +/- 0.6; and 99mTc-HSA, 4.3 +/- 1. In the microorganism group, these ratios were 2.6 +/- 0.6, 3.3 +/- 0.5, 3.4 +/- 0.08, 3 +/- 1.1 and 4.1 +/- 0.6, respectively. Autoradiographic examination of infected tissues indicated that leakage of labeled proteins into interstitial space due to increased capillary permeability may be one of the major mechanisms of uptake.

Animals↗
PubMed1991

The localization of indium-111-leukocytes, gallium-67-polyclonal IgG and other radioactive agents in acute focal inflammatory lesions.

A variety of radioactive agents, injected directly intravenously have demonstrated foci of inflammation by gamma camera imaging, avoiding the in vitro preparation of labeled leukocytes. This study sought to find out if any of these agents mimicked the biodistribution in abscesses and non-target organs of labeled mixed leukocyte suspensions. Eight different agents were compared with 111In-oxine labeled leukocytes in an acute soft tissue E. coli abscess and an acute arthritic lesion in 24 dogs one day after intravenous administration. These included 67Ga-citrate, human and canine polyclonal immunoglobulin (IgG), rabbit anti-dog polyclonal IgG, serum albumin, monoclonal antibody TNT-1 F(ab')2 against nuclear antigens, 57Co-porphyrin and serum albumin nanocolloid. None of these agents achieved abscess concentrations approaching those obtained with labeled leukocytes, and their abscess/blood and abscess/muscle concentration ratios were considerably lower. No statistically significant differences were found between the different radiolabeled proteins evaluated. The abscess concentration of 99mTc-nanocolloid was much lower than that of other agents, and the results with the oldest agent, 67Ga-citrate, were disappointing in these acute experiments.

Abscess↗
PubMed1990

Nuclear medicine comes of age: its present and future roles in diagnosis.

The current role of nuclear medicine in clinical diagnosis was surveyed in a retrospective review of medical records by two internists. About one radiologic imaging study in 20 was a radionuclide procedure, and a somewhat larger fraction was performed in outpatients. The internists found that diagnostic screening procedures in nuclear medicine influenced patient management in 63% of hospital inpatients, and quantitative/monitoring types of tests influenced management in 56%. Of the projected health care costs in the United States of $490 billion, all imaging procedures will account for only $12 billion, and nuclear medicine procedures will account for about $1 billion. Nuclear medicine research continues to blossom. The National Institutes of Health budget for diagnostic imaging research in fiscal year 1988 totaled $86.6 million; nuclear medicine projects represented 43% of this total, all other projects in radiology represented 30%, and projects outside radiology represented 30%. Research with positron emitters and positron emission tomography totaled $20.5 million, and research with radiolabeled monoclonal antibodies totaled $6.2 million. Two major problems may hinder the future practice of nuclear medicine in the United States compared with that in other developed countries: (a) the serious time lag in the approval process for new radiopharmaceuticals by the U.S. Food and Drug Administration and other agencies and (b) the lack of a facility dedicated to the continuous production of radionuclides for biomedical research. Now, there is sporadic production permitted only during high-energy physics experiments. The recent developments which will probably induce the greatest changes in clinical nuclear medicine in the near future are the improvements in design and utilization of single photon emission computed tomographic devices and prolific generation of new radiopharmaceuticals, especially technetium-99m agents for cerebral and myocardial imaging and tumor agents.

Costs and Cost Analysis↗
PubMed1990

Enalaprilat-enhanced renography in a rat model of renovascular hypertension.

The effect of rapid converting enzyme inhibition (CEI) with intravenous enalaprilat on technetium-99m-(99mTc) diethylenetriaminepentaacetic acid (DTPA) and 99mTc-dimercaptosuccinic acid (DMSA) renograms was evaluated in rats with two-kidney, one-clip renovascular hypertension. Rapid sequential DTPA renograms, performed immediately before and five minutes after enalaprilat injection (30 micrograms/kg), demonstrated a selective decrease in clipped kidney DTPA plasma clearance following CEI and no significant effect on unclipped kidney function. Pre- and post-CEI data were obtained with a single injection of DMSA by administering enalaprilat five minutes after the radiopharmaceutical. Enalaprilat slowed the rate of DMSA accumulation in clipped relative to unclipped kidneys, and reduced the clipped/unclipped kidney ratio of absolute DMSA uptake at 10 and 30 min. DTPA and DMSA were equally effective in demonstrating the CEI effect. Enalaprilat was also compared with captopril (3 mg/kg, intraperitoneally), using sequential DTPA renograms. Clipped kidney DTPA plasma clearance was reduced to an identical degree (40%) by both converting enzyme inhibitors. Clinical renographic protocols can probably be devised to take advantage of the rapid, reliable CEI of enalaprilat, thereby shortening total procedure time.

Animals↗
PubMed1990

Thrombus imaging: a comparison of radiolabeled GC4 and T2G1s fibrin-specific monoclonal antibodies.

Radioimmunoimaging of experimentally-induced canine thrombi has previously been achieved with iodine-131- and indium-111-labeled (131I and 111In) anti-fibrin T2G1s monoclonal antibody (MAb). We now compare T2G1s to another anti-fibrin MAb, designated GC4, for imaging fresh and aged canine thrombi. GC4 is specific for a neoepitope exposed on fibrin later in the thrombolytic process after plasmin digestion. Femoral venous thrombi were induced in six groups of dogs, each containing three dogs. In two groups, the MAbs were compared when the thrombi were 3-hr or 3-days old at the time of injection, and the dogs were killed at 48 hr. In thrombi 3-hr-old, the GC4/T2G1s concentration ratio averaged 0.53 compared to 1.9 in 3-day-old thrombi. Two groups of dogs with thrombi 1- or 3-days-old were heparinized before MAb injection and were killed at 24 hr. The heparinized dogs with thrombi 1- or 3-days-old had GC4/T2G1s mean ratios of 2.3 and 2.9, respectively. In the unheparinized groups, the corresponding ratios were 1.1 and 1.9. GC4 may be more useful for clinical thrombus imaging than T2G1s because spontaneous venous thrombi are usually several days old at the time of presentation and patients are often heparinized immediately.

Angiography↗
PubMed1989

Immunoreactivity of 111In and 131I fibrin-specific monoclonal antibody used for thrombus imaging.

Immunoreactivity of radiolabeled F(ab')2 fragment of anti-fibrin T2G1s monoclonal antibody was determined by affinity chromatography using fibrin-coated Sepharose. This preparation is useful for thrombus detection in vivo by gamma camera imaging, provided a high percentage of immunoreactivity is retained after labeling. For 111In labeling, DTPA/F(ab')2 molar ratios were varied from 1000 to 6600/1, with little effect on immunoreactivity. Immunoreactivity of the F(ab')2 fragment, labeled with imaging doses of 131I and 111In, remained high and ranged from 81% to 89%. Equilibrium binding analysis determined the affinity constants of 111In- or 125I-labeled T2G1s and its F(ab')2 and Fab fragments, to be equivalent (Kd approximately 3 X 10(-8) M). This suggests that only one binding domain of T2G1s binds to fibrin even though there are two antigenic sites/mol of fibrin.

Antibodies, Monoclonal↗
PubMed1989

Preferential homing of tumor-infiltrating lymphocytes in tumor-bearing mice.

In view of the current interest in the use of lymphoid cells in adoptive immunotherapy of patients with advanced cancer, we have studied the homing patterns of various lymphoid effector cells in mammary-tumor-bearing mice. Single-cell suspensions of total splenocytes, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were prepared from the spleens of C3H/OuJ mice. Tumor-infiltrating lymphocytes (TIL) were isolated from mammary adenocarcinomas excised from retired breeder females of the same substrain. Effector cells were labeled with indium-111 and injected via a tail vein into female C3H/OuJ mice bearing one or more mammary tumors. Twenty-four hours after administration, total splenocytes, NK cells, and LAK cells distributed themselves evenly between normal mammary tissue and mammary adenocarcinomas. Only TIL had a higher concentration in tumors than in corresponding normal mammary tissue. The ability of the different lymphocyte preparations to lyse YAC-1 cells was determined by means of a 4-h 51Cr-release cytotoxicity assay. Cells harvested from LAK cell cultures and further enriched by centrifugation through a discontinuous Percoll gradient and interleukin-2 (IL-2)-stimulated TIL demonstrated the highest levels of cytotoxicity, while total splenocytes and fresh TIL were characterized by the lowest levels. Since IL-2-stimulated TIL were highly cytotoxic and exhibited better tumor localization than both NK cells and LAK cells in this system, they may be the lymphoid effectors of choice for adoptive immunotherapy of advanced cancer.

Adenocarcinoma↗
PubMed1989

Comparison of different radioactive renal agents in cisplatin-induced tubular toxicity in rats.

The efficacy of five different radiodiagnostic agents for detecting renal tubular dysfunction induced with cisplatin in rats was compared to controls. Diethylenetriaminepentaacetic acid (DTPA) labeled with 99mTc or 111In was administered simultaneously with each of the other four agents [99mTc]glucoheptonate, [99mTc]dimercaptosuccinic acid, [131I]hippuran and [111In]lysozyme) as a standard to normalize for differences in functional impairment from animal to animal from the same dose of cisplatin. The 2-hr plasma clearance and computer-generated 2- to 3-min uptake in the two kidneys with [99mTc]dimercaptosuccinic acid were significantly inferior to similar measurements with the other agents in differentiating abnormal from normal function. The 2-hr uptake of [99mTc]glucoheptonate and [111In]lysozyme proved of no value in this differentiation. The late renal retention of [99mTc]dimercaptosuccinic acid well separated the cisplatin from control rats, but the greatest difference was observed by the 2-hr uptakes of [131I]hippuran and DTPA.

Animals↗
PubMed1988

Evaluation of cyclosporine nephrotoxicity in rats with various renal radioactive agents.

The efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included [99mTc]DTPA, [131I]hippuran, [111In]lysozyme, [99mTc]glucoheptonate (GHA), [99mTc]dimercaptosuccinate (DMS) and [111In]aminated dextran (amdex). A small dose of [99mTc]- or [111In]DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another. There were statistically significant differences in the detectability of the renal functional impairment by plasma clearance, early and 2-hr renal uptake among the different agents. However, none was clearly superior to DTPA. This conclusion is consistent with previous studies which showed a parallel decline in glomerular filtration rate (GFR) and effective renal plasma flow in acute CyA toxicity probably due primarily to vasoconstriction.

Animals↗
PubMed1988

Comparison of different radioactive agents for the detection of renovascular hypertension with captopril in a rat model.

In Goldblatt hypertension in rats produced by implanting a silver clip on the left renal artery, captopril induces a greater difference in the 1-min uptake of diethylenetriaminepentaacetic acid (DTPA) between the two kidneys than in baseline uptakes, similar to the experiences in unilateral renovascular hypertension in man. The combination of captopril and furosemide induces an even greater difference in renal uptakes than with captopril alone in this rat model. In paired experiments, DTPA complexes were used as a standard to compare the differences in renal uptake between the two kidneys after captopril-furosemide with other existing and potential renal radiodiagnostic agents. No statistically significant difference was found between DTPA, glucoheptonate, dimercaptosuccinic acid, aminated dextran, or lysozyme. However, the differences in renal uptake were significantly less with hippuran than with DTPA. Furosemide and captopril caused delayed renal retention of hippuran after one minute. This response appeared to be due to non-specific volume depletion because it occurred in both clipped and unclipped kidneys.

Animals↗
PubMed1988

Migratory patterns of different indium-111 labeled leukocyte populations (chiefly lymphocytes) from control and thymectomized rats.

The blood clearance and 24-hr organ distribution of five lymphocyte-rich suspensions harvested from different source organs were compared in the Wistar rat, after labeling with [111In]tropolone and intravenous injection. Peripheral blood lymphocytes (chiefly T cells) had the highest levels in the blood and lymph nodes, a relatively higher level in intestine and a lower level in the spleen than other suspensions. Thymocytes cleared promptly from the blood, accumulated markedly in the liver, moderately in the spleen, but very poorly in other organs, including the thymus. Splenic cells (rich in B cells) sequestered predominantly in the spleen and liver. Splenic cells nonadherent to nylon wool (T-cell enriched) had a relatively high uptake in lymph nodes and marrow. Splenic cells from thymectomized rats (NK cell enriched) localized predominantly in the liver and spleen, and poorly in lymph nodes. We conclude that the source organ for harvesting rat lymphocytes is an important determinant in their localization, as well as other factors such as the techniques of isolation, the toxicity and stability of the radioactive label and the cell radiation dose from internalized radioactivity.

Animals↗