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Biomedical subjects

M Frier

Publications and source records attributed to M Frier.

At least 37 records · Page 2Linked to original sources
PubMed1997

Bedside nuclear medicine investigations in the intensive care unit.

The functional nature of nuclear medicine procedures makes them especially valuable in the management of patients undergoing intensive care. However, the severe nature of the patient's condition invariably prevents him or her from attending the nuclear medicine department for diagnostic investigations. We have piloted a bedside nuclear medicine service using a four-probe detector system linked to an IBM computer with curve processing software. Protocols for a range of radionuclide probe investigations, including renal, hepatobiliary, gastric outflow and lung vascular permeability, using 99Tcm and 111In radiopharmaceuticals have been established. The measurement of lung vascular permeability in patients with clinical symptoms of adult respiratory distress syndrome was considered to be a valuable procedure on the intensive care unit. Due to the poor availability of 113Inm, which had previously been used for the measurement of lung permeability, we used a technique based on in vivo labelling of serum transferrin with 111In-chloride together with 99Tcm-red blood cells for the calculation of the plasma protein accumulation index. Other procedures include the measurement of gastric outflow in patients previously on parenteral feeding, and the assessment of hepatobiliary and renal function. The equipment proved to be reliable and convenient for use at the bedside, although ultrasound imaging was essential for the correct positioning of the probe detectors over smaller organs such as the kidneys and the gallbladder. The high sensitivity of the probe detectors required only low administered amounts of activity, minimizing radiation protection measures for patients and staff. The administration of radiopharmaceuticals via indwelling lines and tubes presented particular problems and we recommend that parenteral injections should not be given through manifold giving set, or via Teflon cannulae.

Adult↗
PubMed1997

To report or not?

Explore the source record for details and available documents.

Adolescent↗
PubMed1997

Human biodistribution of an ultrasound contrast agent (Quantison) by radiolabelling and gamma scintigraphy.

The biodistribution and kinetics of an air filled human serum albumin microcapsule formulation (Quantison) intended for use as an intravenous ultrasound contrast agent have been examined. 12 healthy subjects were administered with approximately 50 million microcapsules per kilogram body weight, radiolabelled with 50 MBq 123I. Imaging was performed over a period of 58 h using a large field-of-view gamma camera and the amount of labelled material present in the blood, urine and faeces measured. Imaging demonstrated that the liver was the organ with the highest uptake, with a mean uptake of 41.8% (SD 10.4%) of the administered dose 1 h following administration. The maximum uptake of the agent in the lungs was low, mean 4.0% (SD 3.4%). A small amount of uptake was visible in the bone marrow; however, this was not quantifiable. There was also evidence of minimal myocardial activity within 5 min of administration. No adverse events were observed and there were no changes in any of the individual post-study indices. The present study demonstrates the safety of Quantison. Gamma scintigraphy played a useful role in confirming the biodistribution of the agent with little lung uptake, high liver uptake and evidence of myocardial uptake.

Adult↗
PubMed1996

Biodistribution of (111)indium-labeled engineered human antibody CTMO1 in ovarian cancer patients: influence of protein dose.

Thirty-one patients suspected of having ovarian cancer received a single i.v. injection of radiolabeled (100 MBq (111)In) engineered human CTMO1 (hCTMO1) to investigate its potential as an internalizing drug carrier. hCTMO1 is a complementary-determining region-grafted human IgG4 monoclonal antibody recognizing an ovarian carcinoma-associated antigen, the MUC-1-gene product. The amount of radioactivity was determined in tumor tissue, various normal tissues, including liver biopsies, and blood samples obtained at laparotomy, 6 days after injection of either 0.1 or 1.0 mg hCTMO1/kg of body weight. Circulating antigen-15-3 was measurable in all patients before injection, and immune complex formation was already present at the end of infusion. In the 0.1 mg/kg group, most of the radioactivity was bound to immune complexes, whereas in the 1.0 mg/kg group, most was bound to IgG monomers. Increasing the hCTMO1 dose 10-fold did not influence the overall disappearance of (111)In from the blood, but the elimination half-life of (111)indium bound to immune complexes was increased 2-fold. Uptake in tumor tissue 6 days postinjection at the 0.1 mg/kg dose was 7.6 times higher (P = 0.0009) than in normal tissue and 2.5 times higher (P = 0.03) than in blood. At the 1.0 mg/kg dose, the uptake in tumor tissue was 14.0 times higher (P = 0.0003) than in normal tissue and 8.1 times higher (P = 0.0007) than in blood. Liver activity was substantial (23.7 +/- 10.5 and 18.3 +/- 6.7% of the injected dose/kg for the 0.1 and 1.0 mg/kg dose group, respectively). These results are superior to those found with other clinically tested anti-MUC-1 gene product antibodies. hCTMO1 seems to be a suitable carrier for cytotoxic agents in ovarian carcinoma patients; the better uptake results and tumor-to-blood ratios are obtained at the higher dose of 1.0 mg hCTMO1/kg body weight.

Adult↗
PubMed1996

Nuclear medicine techniques in the evaluation of pharmaceutical formulations.

Nuclear medicine imaging techniques have great potential in the study of the behaviour of drug formulations and drug delivery systems in human subjects. No other technique can locate so precisely the site of disintegration of a tablet in the G1 tract, the depth of penetration of a nebulised solution into the lung, or the residence time of a drug on the cornea. Using the gamma camera to image the in vivo distribution of pharmaceutical formulations radiolabelled with a suitable gamma emitting radionuclide, images may be used to quantify the biodistribution, release and kinetics of drug formulations and delivery from novel carrier systems and devices. Radionuclide tracer techniques allow correlation between the observed pharmacological effects and the precise site of delivery. The strength of the technique lies in the quantitative nature of radionuclide images. Such studies not only provide data on the nature and characteristics of a product, such as reliability and reproducibility but, may also be used in submission to Regulatory Authorities in product registration dossiers.

Chemistry, Pharmaceutical↗
PubMed1996

Stability of radiopharmaceuticals during administration to the intensive care patient.

Nuclear medicine can provide useful data when monitoring the organ function of patients undergoing intensive care. Test procedures involve the administration of radiopharmaceuticals and external monitoring using gamma cameras or nuclear probes. The radiopharmaceuticals required may be given at lower doses than normally used in routine nuclear medicine imaging, are ideally available 24 h a day and are preferably administered via indwelling cannulae and giving sets. Three radiopharmaceuticals have been studied; a renal function agent, a hepatobiliary function agent and a product used for in vivo labelling of protein for lung permeability studies. Under conditions of storage, dilution and passage through giving sets (simulating conditions found during administration in the intensive care setting), some instability can be demonstrated in each product, which could result in the tests giving rise to wrong or misleading data. It is recommended that radiopharmaceuticals are not diluted excessively, and that where possible, parenterally-administered products are given by direct intravenous injection and not through giving sets.

Critical Care↗
PubMed1995

Targeting of bladder cancer with monoclonal antibody NCRC48--a possible approach for intravesical therapy.

OBJECTIVE: To determine the localization of the anti-MUC1 mucin monoclonal antibody (mAb) NCRC48 to bladder cancer following intravesical administration. PATIENTS AND METHODS: mAb NCRC48 (330-500 micrograms) radiolabelled with 111indium (11-17 MBq) was administered intravesically to 12 unselected patients with radiological evidence of bladder cancer. Tumour localization was assessed by gamma-camera imaging and by tissue biodistribution studies on biopsies obtained at cystoscopy at about 2 or 24 h after the procedure. After 24 h, whole blood radioactivity was measured and 3 weeks after the procedure the serum level of human anti-mouse antibodies was estimated using an ELISA method. RESULTS: Eleven patients had tumours confirmed at cystoscopy (grades 1-3, stages pTa-pT2). The mean uptake of NCRC48 by tumour and by normal urothelium (expressed as the percentage of the instilled dose/g x 10(3) +/- SD) at 2 h was 3.42 +/- 3.68 and 0.41 +/- 0.77 (P < 0.05). After 24 h, the values for tumour and normal urothelium were 1.17 +/- 1.18 and 0.17 +/- 0.11, respectively. Areas of increased activity on the scintigrams were consistent with the position of the tumours at cystoscopy. No radioactivity was detected in blood at 24 h and there was no evidence of a human anti-mouse antibody response. CONCLUSION: The MUC1 mucin may be a suitable antigen to study the potential of therapeutic strategies based on monoclonal antibody targeting of superficial bladder cancer and may allow the development of more effective agents in the treatment of this condition.

Aged↗
PubMed1995

Effect of bran particle size on gastric emptying and small bowel transit in humans: a scintigraphic study.

Bran is an effective treatment for constipation but its use is often limited by heartburn and bloating. This study examined the effect of fine and coarse bran (15 g) on the gastric emptying and small bowel transit of a 325 kcal rice test meal. Twelve healthy volunteers underwent a three way cross over study, ingesting the technetium-99m labelled rice meal with or without 15 g of indium-111m labelled fine or coarse bran, in random order. Serial scintigraphic images were obtained to define gastric emptying and colonic arrival of label. Compared with control values (99 (9) minutes) (mean (SEM)), the time to 50% gastric emptying was significantly delayed by coarse but not fine bran, being 121 (6) and 104 (9) minutes respectively, p < 0.05, n = 12. Fundal emptying was unchanged but both brans seemed to increase the proportion of isotope in the antrum at 90 minutes. Small bowel transit was slightly faster with both bran types but in this study the difference was not significant. Both the bran and rice labels moved down the gut without significant separation. Fine bran causes less disturbance of gastric physiology than coarse bran.

Adult↗
PubMed1994

Experimental biodistribution studies of 99mTc-recombinant human serum albumin (rHSA): a new generation of radiopharmaceutical.

Recombinant human serum albumin (rHSA) produced by cultured fermentation has been prepared in the form of microcapsules nominally 3-5 microns in diameter and radiolabelled with technetium-99m following reduction with stannous chloride. Radiochemical purity was assessed by chromatography on instant thin-layer chromatography and found to be greater than 90%. No evidence of aggregation was seen by microscopic examination. Imaging biodistribution studies in New Zealand white rabbits demonstrated targeting to the liver or lung, respectively, depending upon the size and surfactant properties of the microcapsules. This communication is the first to show scintigraphic studies using 99mTc-labelled rHSA with the potential for lung, liver and cardiovascular imaging and demonstrates that recombinant DNA technology offers an important new source of materials suitable for use as radiopharmaceuticals without the need for pooled human blood products.

Animals↗
PubMed1994

Radiopharmaceuticals and the gastrointestinal tract.

A review is presented of the design of radiolabelled test meals for the evaluation of gastrointestinal function, including oesophageal transit, gastro-oesophageal reflux, gastric emptying, enterogastric reflux and transit through the whole bowel. Descriptions of different systems are presented, together with validations of the procedures used. Published methods for assessment of oesophageal transit show a marked degree of consistency, whereas gastric emptying studies employ a wide range of both liquid and solid test meals. Recommendations are made concerning the optimal system for investigation of each part of the gastrointestinal tract, but whichever system is adopted, it is important to employ some validation procedures, and to establish normal ranges in the population under study.

Bile Reflux↗
PubMed1994

Leucocyte radiolabelling techniques: practical aspects.

Radiolabelled leucocytes migrate rapidly to sites of acute inflammation. The simplest technique for imaging intestinal inflammation involves radiolabelling patients' mixed while cells ex vivo with either 99mTc or 111In which are then reinjected. However, further purification of mixed white cells to granulocytes is needed for optimal results using 111In. Owing to the simpler labelling procedure, availability, image quality and dosimetry, 99mTc-HMPAO has gained favour for the investigation of acute inflammation including inflammatory bowel disease. Because of its longer half life. 111In is more suited to the imaging of chronic inflammation such as osteomyelitis. Attempts to radiolabel granulocytes in vivo using monoclonal anti-granulocyte antibodies have been largely unsuccessful to date, and this approach remains a challenge for the future.

Cell Separation↗
PubMed1992

Monoclonal antigranulocyte antibody imaging in inflammatory bowel disease: a preliminary report.

The 99Tcm-labelled antigranulocyte antibody BW250/183 has been used in the detection of intestinal inflammation in patients with active ulcerative colitis and Crohn's disease. Planar images were obtained up to 24 h after intravenous injection of the antibody. Eight out of nine patients with ulcerative colitis and six out of seven patients with Crohn's disease gave positive images. In 11 patients distribution of the inflammation was confirmed by barium studies, colonoscopy or surgery, whilst in two the antibody scan suggested more extensive disease than barium enema. None of the patients had any adverse reactions. Imaging with BW250/183 appears to give an accurate indication of the extent of inflammation in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed1991

Double-blind randomized trial of perioperative fibrinolytic enhancement for femoropopliteal bypass.

Patients with rest pain or acute peripheral arterial thrombosis are known to have impaired endogenous fibrinolysis, which is associated with an increased risk of early vascular graft thrombosis. This risk is exacerbated by the fibrinolytic shutdown which is known to occur after major surgery. Stanozolol, which has been demonstrated to enhance endogenous fibrinolysis, was therefore used in an attempt to prevent this perioperative fibrinolytic shutdown and so enhance graft patency. Twenty-seven patients were randomized to receive either 50 mg stanozolol or placebo intramuscularly 24 h before operation, followed by a 6 week course of either 5 mg stanozolol or placebo orally, twice daily. On the second day after operation, 10-11 MBq of autologous 111indium-labelled platelets were injected, with scanning over the graft on the 3 following days. Despite using a large depot of stanozolol, significant effects, such as raised plasminogen (P less than 0.001), reduced fibrinogen (P less than 0.001) and reduced euglobulin lysis time (P less than 0.001), were not seen until the seventh day after operation, with maximum benefit at 6 weeks. This was reflected in the 111indium-labelled platelet deposition studies. The placebo group had a progressive increase in platelet deposition on all 3 days. In contrast, those receiving stanozolol showed a lower, static picture of deposition. However, these changes did not attain statistical significance. Three patients experienced early graft thrombosis, two in the placebo group and one in the stanozolol group. Only an incomplete inhibition of the perioperative fibrinolytic shutdown was achieved. Much longer preoperative courses are thus required to allow the maximum effect to be present at the most crucial time. At present, perioperative fibrinolytic enhancement does not appear to be a practical proposition, and we must await the development of new safer and more potent agents.

Aged↗
PubMed1991

Detection and characterization of arterial thromboses using a platelet-specific monoclonal antibody (P256 Fab').

Arteriography does not reliably distinguish between acute and chronic arterial occlusions. Seventeen patients with acute lower limb ischaemia were investigated by arteriography and by imaging with a platelet-specific monoclonal antibody (P256 Fab'); 20 MBq 111In-labelled P256 Fab' was administered intravenously and patients were imaged at intervals of between 20 min and 24 h. Thirteen patients were subsequently treated with intra-arterial thrombolysis. In six the images showed foci of increased uptake of 111In-labelled P256 Fab' and the corresponding arterial segment was recanalized. Patency to 30 days was maintained in four cases. Seven patients had negative scans, only four of whom achieved lysis, and two of these suffered early rethrombosis. The remaining four patients were excluded from thrombolysis by the arteriographic appearances. 111In-labelled P256 Fab' imaging can identify sites of acute arterial thrombosis and may have clinical applications in the management of peripheral vascular disease. Further studies are required to test whether the technique has a role to play in patient selection for thrombolysis.

Antibodies, Monoclonal↗
PubMed1991

Anomalies in reduction-mediated technetium-99m labelling of monoclonal antibodies.

A reduction-mediated technetium-99m labelling method has been evaluated with a range of tumour-specific monoclonal antibodies. Antibodies reduced with 2-mercaptoethanol (2-ME) had free sulphydryl groups, but their number was much higher than could be accounted for by only limited intra-chain reduction of disulphide bonds. Reduced antibody could be labelled efficiently with 99mTc using an methylene diphosphonate (MDP) bone-scanning kit, although this seemed to depend on the presence of residual 2-ME in the preparations. With a carcinoembryonic antigen (CEA)-specific antibody, immunoreactivity of labelled antibody was confirmed, and after injection into nude with CEA-producing xenografts there was localisation into the tumours. Sephacryl S300 gel filtration showed the radiolabel eluting at a single discrete peak at the expected 150 kDa. However, examination of all of the labelled antibodies by polyacrylamide gel electrophoresis (PAGE) and autoradiography showed the presence of a large number of radiolabelled low molecular weight degradation products of the antibodies. These degradation products seemed to be formed in previously reduced antibodies during processing for PAGE, indicating some fragility of the reduced antibody.

Antibodies, Monoclonal↗
PubMed1991

A comparison of same day and separate day injection protocols for myocardial perfusion SPECT using 99Tcm-MIBI.

Three dose administration protocols for 99Tcm-MIBI were applied to groups of 15 patients with known or suspected ischaemic heart disease. Firstly, injections were given on consecutive days, with 300 MBq at rest and 500 MBq 24 h later at exercise. Secondly, both injections on the same day with 200 MBq at rest followed 1.5 h later by 1000 MBq during exercise. Finally, both injections on the same day with 200 MBq at rest followed 1.5 h later by 600 MBq during exercise. The diagnostic accuracy was significantly better when the administrations were on separate days than when given on the same day. There was no difference in diagnostic accuracy between the two same day protocols. The same day protocols gave a significantly higher false negative reporting rate than the separate day protocol.

Adult↗
PubMed1990

111In platelet deposition following peripheral arterial thrombolysis.

Streptokinase (Sk) and recombinant tissue plasminogen activator (rt-PA) have widely different effects on platelet aggregation. We have therefore undertaken a prospective evaluation of the deposition of indium-111 platelets following peripheral arterial thrombolysis. Seventeen patients were studied using autologous indium-111 labelled platelets. Patients were randomly allocated to receive 0.5 mg h-1 intra-arterial rt-PA (ten patients), or 5000 units h-1 Sk and 250 units h-1 heparin intra-arterially (seven patients). Initial uptake ratios (comparing affected limb to contra-lateral limb) at 24 h were usually low for both agents (medians: Sk 1.17; rt-PA 1.20) despite previous angioplasty or extensive thrombosis. There were minimally higher uptake ratios at 48 h and 72 h following Sk (1.64-1.45), than with intra-arterial rt-PA (0.93-1.43). Overall, two patients (one from each group) failed to achieve complete lysis or incurred early rethrombosis. Both were associated with a progressive increase in uptake ratio which was not present in those patients with successful initial lysis and continued patency at 30 days (1.18-0.94-1.19). We have been unable to demonstrate any significant difference in post-lysis platelet deposition between intra-arterial streptokinase and recombinant tissue plasminogen activator in this preliminary study. However, higher platelet deposition was associated with failure to achieve complete lysis and early rethrombosis. Concurrent therapy with antiplatelet agents may therefore be indicated in these patients.

Blood Platelets↗