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Biomedical subjects

S J Mather

Publications and source records attributed to S J Mather.

At least 73 records · Page 4Linked to original sources
PubMed1992

A pharmacological guide to medicines which interfere with the biodistribution of radiolabelled meta-iodobenzylguanidine (MIBG).

Radiolabelled meta-iodobenzylguanidine (MIBG) is widely used in the diagnosis, follow-up and treatment of patients with tumours of neural crest origin. Some commonly prescribed and readily available over-the-counter medicines interfere with the uptake and biodistribution of this radiopharmaceutical. This may lead to poor concentration of radiolabelled MIBG within the target organs and tissues. The clinical implications are a potentially inaccurate assessment of tumour burden during diagnostic studies and a suboptimal radiation dose when MIBG is employed for targetted radiotherapy. In order to avoid false negative results a comprehensive list of prescribed and over-the-counter medicines that have the potential to inhibit uptake of MIBG has been compiled. It is hoped that this will help nuclear medicine physicians to avoid this pitfall.

3-Iodobenzylguanidine↗
PubMed1992

Pituitary imaging using a labelled somatostatin analogue in acromegaly.

OBJECTIVE: A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I-labelled Tyr3-octreotide analogue of somatostatin in the visualization and functional characterization of growth hormone-secreting pituitary adenomas. PATIENTS: Fifteen patients with biochemically-proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics. MEASURES: Planar and single-photon-emission computerized tomographic (SPECT) images of the head were obtained using a gamma-camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 micrograms octreotide. RESULTS: Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients in whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning. CONCLUSIONS: Uptake of 123I-labelled Tyr3-octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.

Acromegaly↗
PubMed1991

Diagnostic evaluation of 111In and 99mTc radiolabelled monoclonal antibodies in ovarian and colorectal cancer: correlations with surgery.

The results of radioimmunoscintigraphy, RIS, in colorectal and gynaecological cancers were related to the surgical findings and the analysis of the surgical specimens. The improvement in the accuracy of RIS with the progression from 111In through 123I to 99mTc as radiolabel is demonstrated. The convenience, low cost and low radiation dose of 99mTc-labelled antibodies brings the technique of RIS into routine use in the management of patients with these cancers.

Adult↗
PubMed1991

Radiolabelled monoclonal antibodies in oncology. I. Technical aspects.

The principles and technique of radioimmunoscintigraphy are described with particular reference to the choice of antibody and the radiolabel, the radiolabelling procedure and the patient protocols. The arguments in favour of using a short-lived high count rate radionuclide for radioimmunoscintigraphy are set out. Methods for labelling monoclonal antibodies with 111In, 123I or 99Tcm are described. The early image at 10 min after injection is essential as it acts as a template with which later images may be compared. In conclusion, many of the technical aspects of radioimmunoscintigraphy have been overcome and it is ready for wider application in oncology patients.

Antibodies, Monoclonal↗
PubMed1991

The design of a two-phase radiolabelled meal for gastric emptying studies.

A meal intended for use in gastric emptying studies must be highly reproducible, must provide a normal physiological stimulus in terms of bulk, calorie content and composition and must employ stable radiotracers which accurately reflect in their biodistribution, the fate of the two phases. This is particularly important in a field, such as gastric emptying, where so many variables may influence the results. A conventional pancake and orange juice were chosen as suitable vehicles for the solid and liquid phases. 111In-labelled resin beads were used as the solid-phase marker and a variety of 99Tcm-labelled radiopharmaceuticals including pertechnetate, DTPA and colloid forms were investigated as liquid-phase markers. Prior to administration to patients, the stability of the phases and their interactions in vitro were investigated. The use of 99Tcm-DTPA resulted in a loss of 111In from solid to liquid phase. All non-colloidal markers exhibited a tendency for adsorption onto solid phase. Colloidal markers including rhenium and antimony sulphide colloids showed the truest delineation of the liquid phase.

Drinking↗
PubMed1990

Radioimmunoscintigraphy of ovarian tumors using a new monoclonal antibody, SM-3.

Radioimmunoscintigraphy with SM-3 monoclonal antibody produces results similar to those obtained with 123I-labeled HMFG-2. The tumor specificity of SM-3 in vitro is not as marked as that in vivo. SM-3 is, however, much easier to produce in tissue culture and, with the availability of 99mTc labelling, has allowed radioimmunoscintigraphy to be done as an outpatient procedure. This technique has important implications for the continuing management of patients with ovarian cancer.

Adult↗
PubMed1990

Postoperative analgesia after paediatric orchidopexy: evaluation of a bupivacaine-morphine mixture.

The value of combining morphine with bupivacaine for caudal analgesia was investigated. Thirty children, undergoing orchidopexy, received a caudal block of 0.125% bupivacaine with or without morphine 0.05 mg kg-1. Analgesia, side-effects, ventilatory frequency and oxygen saturation (SaO2) were recorded after operation. None of the 15 patients receiving the bupivacaine-morphine mixture required post-operative opioids, whereas eight of 15 patients receiving bupivacaine alone needed additional opioid analgesia. The incidence of side effects after surgery was similar for the two groups and there was no detectable difference in ventilatory frequency or SaO2.

Analgesia, Epidural↗
PubMed1990

Radioimmunoscintigraphy of orbital metastases from ovarian carcinoma.

Radioimmunoscintigraphy with I-123 labeled monoclonal antibody HMFG1 has been used for imaging primary and metastatic ovarian neoplasms. Uptake of I-123 labeled HMFG1 is reported in a patient with an orbital metastasis from a primary ovarian adenocarcinoma. Radioimmunoscintigraphy may have a role to play in imaging metastatic orbital neoplasms.

Adenocarcinoma↗
PubMed1990

99mTc radioimmunoscintigraphy of colorectal cancer.

The monoclonal antibody PR1A3 against a normal colonic columnar cell surface antigen has been labelled with 99mTc and used for imaging colorectal cancer. High uptake in undifferentiated cancer is seen. The tumour to mucosa ratio was up to 63:1 and the percentage of the injected activity in the tumour up to 1.7 X 10(-2%)g-1. As 99mTc is continuously available in a Nuclear Medicine Department, on receipt of a request the study may be completed within 24 h enabling radioimmunoscintigraphy to be used routinely in the management of patients with colorectal cancer.

Adenocarcinoma↗
PubMed1990

Reduction-mediated technetium-99m labeling of monoclonal antibodies.

A simple and generally applicable method for labeling antibodies with technetium-99m (99mTc) is described. Following reduction of intrinsic disulphide bonds, the antibody is labeled with 99mTc in the presence of a weak competing ligand methylene diphosphonate. High labeling efficiencies (greater than 97%), in a final labeling step taking only a few minutes, can be routinely obtained with high in-vitro stability over 24 hr. No effect upon antibody reactivity is seen.

Animals↗
PubMed1989

Labelling monoclonal antibodies with yttrium-90.

Using the cyclic DTPA derivatisation procedure developed by Hnatowich, conditions have been optimised for labelling three tumour-associated monoclonal antibodies with 90Y. High labelling efficiencies (greater than 95%) at modest specific activities (1 mCi/mg) could be routinely obtained. Radiochemical stability of the radiolabelled preparations in vitro was good, but radiolysis resulted in early losses of antibody immunoreactivity.

Antibodies, Monoclonal↗
PubMed1988

Monoclonal antibodies to placental alkaline phosphatase: preclinical evaluation in a human xenograft tumour model of F(ab')2 and Fab fragments.

Six new placental alkaline phosphatase monoclonal antibodies (MAbs) have been evaluated in order to select a potentially clinically useful antibody fragment for use in immunoscintigraphy or therapy. Initially, 3 antibodies were identified by trial pepsin digestion as likely to give satisfactory F(ab')2 yield. The corresponding intact antibodies were then compared for ability to localise human xenograft tumours in athymic mice. Of the best of these, designated 3F6, F(ab')2 and Fab fragments were then evaluated in similar xenograft experiments. In intact antibody biodistribution comparisons, 3F6 showed good tumour retention and satisfactory specific/non-specific ratios at 8 days. In similar fragment biodistribution experiments 3F6 F(ab')2 gave the highest tumour/blood ratio (10) and tumour/organ ratios (19) and the best specific/non-specific localisation. This fragment also showed higher absolute uptake in the tumour than intact antibody, 18.9% and 14.4% respectively of the injected dose. As expected, fragments showed much faster blood clearance rates than whole antibody. For Fab the in vivo instability by 6 hr was also demonstrated.

Alkaline Phosphatase↗
PubMed1988

A rapid method for the preparation of 99Tcm hexametazime-labelled leucocytes.

99Tcm (+/-)-hexamethylpropyleneamineoxime (HMPAO) (99Tcm Hexametazime) has been recently reported as an alternative for labelling leucocytes. For reasons of convenience, radiation dose and image quality, many workers have welcomed this novel approach except for its complicated labelling protocol and venesection of 100 ml. This technique has been modified to give a simpler routine in-house labelling technique. It has three advantages: only about 20 ml of blood is required, the labelling time is just under 1 h and high yields of labelled leucocytes are obtained (mean of 500 MBq per injection dose). The properties of labelled leucocytes using this modified method are; 80% granulocyte-bound radioactivity, a rapid lung transit and a blood granulocyte recovery of 40% at 30 min similar to those described previously. The viability of the labelled leucocytes was tested and confirmed in vitro using a migration technique and in vivo by showing no lung retention on early imaging and high splenic uptake. A rapid in-process chromatography assessment procedure for regulating the protocol has been developed. Successful abscess imaging by 4 h has been achieved in 21 patients with normal results in another 22 patients without abscesses. This simpler method should encourage a more widespread application of scintigraphy using radiolabelled granulocytes.

Humans↗
PubMed1988

Kinetic analysis and probability mapping applied to the detection of ovarian cancer by radioimmunoscintigraphy.

Kinetic analysis with probability mapping is an objective method of serial image analysis applicable to radioimmunoscintigraphy. The technique is described and subjected to clinical testing by comparing the prediction of biopsy histology from the probability map in patients coming to operation. In those with ovarian cancer undergoing second-look laparotomy after completing full courses of chemotherapy, the prediction of histology in 108 biopsy sites was 45 true positives and 38 true negatives, sensitivity 80%, specificity 73%, accuracy 77% p less than 0.001. In patients with tumors less than 2 cm diameter, 41 biopsy sites were predicted with a specificity of 78% and an accuracy of 76%, p less than 0.01. The technique is reducing the need for second-look laparotomy in patients with subclinical and subradiological disease. Such disease is suitable for intraperitoneal radioimmunotherapy.

Adult↗
PubMed1987

Localization of radioiodine conjugated to the monoclonal antibody HMFG2 in human ovarian carcinoma: assessment of intravenous and intraperitoneal routes of administration.

The localization of i.p. injected, radioiodine conjugated monoclonal antibody HMFG2 was studied in 18 patients with ovarian carcinoma. Patients were injected i.p. at time points up to 168 h before laparotomy, at which time tumor, ascites, normal tissue, and blood samples were removed and the contained radioactivity measured. In the first 10 patients, localization was compared with that of a simultaneously injected irrelevant (nonspecific) antibody (UJ13A) of the same immunoglobulin class and, in the subsequent 8 patients, with HMFG2 administered i.v. After i.p. injection, HMFG2-radioiodine was found in concentrations of 0.0001-0.0030% of the injected amount per gram in solid tumor, 0.0363-0.02560%/g in ascites, 0.0003-0.0017%/g in blood, and 0.001-0.0012%/g in normal tissue. Tumor:normal tissue ratios of 0.9-10.0 and tumor:blood ratios of 0.3-4.0 were seen up to 168 h after injection. Localization of the HMFG2 conjugate was consistently greater than that of the irrelevant antibody. For solid tumor, the i.v. route of administration resulted in consistently higher absolute levels of HMFG2 conjugate uptake but tumor:blood and tumor:normal tissue ratios were similar. On the other hand the i.p. route of administration offered consistent advantages of 4- to 71-fold over the i.v. route when HMFG2 conjugate localization on ascites cells was examined. Ascites:normal tissue and ascites:blood ratios of up to 512 and 448, respectively, were achieved. After i.p. injection, radioiodine was cleared from the body exponentially with a half-life of 50 h. Maximum circulating blood levels of 8.6 +/- 2.0% injected activity were seen at 48 h and these then decreased with a t 1/2 value of 38 h. Over 80% of injected activity was cleared in the urine as nonprotein bound iodine by 168 h.

Antibodies, Monoclonal↗
PubMed1987

Identification of immunoreactive monoclonal antibody fragments for improved immunoscintigraphy.

Results obtained in animal models suggest that antibody fragments may have advantages over whole immunoglobulin for in vivo localisation studies. Proteolytic digestion of monoclonal antibodies may however yield a mixture of products unsuitable for in vivo use. This report describes a method whereby the immunoreactive products of antibody digestion can be identified by probing nitrocellulose blots of the gel-separated digest with the specific antigen. Optimum conditions for the production of the reactive fragments can then be determined and once identified they can be purified to homogeneity. Using this method conditions have been defined for the production of F(ab)2 and Fab fragments from a papain digest of an antibody to placental alkaline phosphatase (H17E2). In this case the antigen has enzyme activity which can be used to detect binding to the immunoreactive bands on the Western blots. In vivo experiments in nude mice carrying xenografts of a tumour expressing the H17E2 reactive antigen were performed to determine the efficacy of localisation of the purified fragments as compared to the whole antibody. As expected the absolute levels of radioactivity localised in the tumour was highest using whole antibody, whereas the F(ab)2 fragments produced the highest tumour:blood ratios.

Alkaline Phosphatase↗