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Biomedical subjects

A C Perkins

Publications and source records attributed to A C Perkins.

At least 109 records · Page 6Linked to original sources
PubMed1990

Mouse-specific antibody responses to a monoclonal antibody during repeated immunoscintigraphy investigations: comparison of antibody titres and imaging studies in a rat model.

As a model for human mouse-specific antibody responses in patients undergoing immunoscintigraphy, we have investigated in rats the production of mouse-specific antibodies (MA) to the mouse monoclonal antibody 791T/36. At intervals of between 5 and 16 weeks the rats were given repeated cycles of intravenous (IV) injections of antibody with or without a simultaneous intradermal (ID) injection. The IV dose was 60 micrograms/kg, a dose similar to that used in many clinical immunoscintigraphy studies. The ID injection was 2 micrograms, which mimicks the skin test dose often given in clinical imaging protocols. The study was carried out with both 131I-labelled antibody and with antibody labelled with 111In by diethylenetriamine-penta-acetic acid (DTPA) chelation. MA was measured with a passive haemagglutination assay using sheep red blood cells coated with the monoclonal antibody. Of rats given ID injections of unlabelled antibody at the same time as the IV imaging doses, 9/20 produced MA during 4 cycles of injections. In contrast, only 2/16 rats given only the IV dose produced MA. Both 131I- and 111In-labelled antibody appeared equally immunogenic with 5/18 and 6/18 overall responders, respectively. The production of MA was associated with a significant perturbation in the biodistribution of the IV dose of labelled antibody as seen by gamma-camera imaging of the rats given 111In-labelled antibody. There was clearance of immune complexes to the liver, this organ accumulating up to 90% of the whole body count rate of radiolabel. MA titres of between 1/100 and 1/78,000 caused equal perturbation of biodistribution, although below 1/100 the effect was more variable.

Animals↗
PubMed1990

Multi-centre immunoscintigraphic study using indium-111-labelled CEA-specific and/or 19-9 monoclonal antibody F(ab')2 fragments.

Six European nuclear medicine centres performed immunoscintigraphy first retrospectively in 34 patients using indium-111-labelled carcinoembryonic antigen (CEA)-specific and/or 19-9 F(ab')2 fragments. Results for sensitivity and specificity in tumour sites were 94% and 87%, respectively, for the pelvis and 73% and 100% for the extrahepatic abdomen. A second prospective series concerned 58 other patients previously operated on for colorectal adenocarcinoma (27 colon, 31 rectum). Two-thirds of these patients had a suspected recurrence signalled by an isolated rise in tumour markers, and 46 patients examined by immunoscintigraphy, X-ray computed tomography and ultrasonography were found to have a recurrence (a total of 62 tumour sites). Sensitivity and specificity with immunoscintigraphy were 90% and 97%, respectively, for the pelvis and 62% and 95% for the extrahepatic abdomen. For 29 patients injected with CEA-specific fragments, sensitivity was 90% and specificity 94% for the pelvis. For 25 patients injected with 19-9 fragments, pelvic sensitivity and specificity were 80% and 100%, respectively, whereas sensitivity for the extrahepatic abdomen was only 29% since several cases of peritoneal carcinosis were not visualized. In the prospective series, comparison of the three imaging techniques for all tumour sites (including liver and in 5 cases thorax) gave a sensitivity and specificity of 82% and 91%, respectively, for immunoscintigraphy, 52% and 95% for X-ray computed tomography and 59% and 100% for ultrasonography. These results thus confirm the advantage of using 111In-labelled CEA-specific or 19-9 to visualize and localize recurrences of colorectal cancer.

Adenocarcinoma↗
PubMed1990

A prospective evaluation of OC125 and magnetic resonance imaging in patients with ovarian carcinoma.

Eighteen patients with suspected primary or recurrent ovarian carcinoma have been investigated in each case by the assay of serum levels of the antigen CA125, immunoscintigraphy using 131I-OC125 antibody and magnetic resonance imaging using a 0.15 Tesla system. The final diagnosis was confirmed by laparotomy or laparoscopy. Serum levels of CA125 ranged between 5 and 780 units/ml (normal range less than 35). Antibody images and MRI were truly positive in 11 patients, 2 of whom were subsequently found to have bowel tumours. MRI showed greater detail of smaller lesions whilst immunoscintigraphy was more suited to the detection of distant metastases. In 7 patients the antibody images were positive whilst the serum marker levels were normal. This pilot study provides a preliminary comparison of the more recent techniques currently being evaluated for the detection of ovarian carcinoma.

Adult↗
PubMed1990

Automated volume determination of the liver and spleen from Tc-99m colloid SPECT imaging. Quantification of the liver functional and nonfunctional tissue in disease.

An automated volume determination program using SPECT imaging with Tc-99m has been validated by both phantom and patient studies. Its use for monitoring change of function of the liver and change in tumor mass during different therapy regimes has been assessed. The technique is not restricted to the estimation of the hepatic functioning tissues; it therefore has many potential clinical implementations for volume determination in other organs.

Humans↗
PubMed1990

Hepatic perfusion index in the diagnosis of overt metastatic colorectal cancer.

The hepatic perfusion index (HPI) was measured in 180 patients with colorectal cancer: 109 with primary colorectal cancer, 38 with suspected recurrent colorectal cancer and 33 following curative resection of colorectal cancer. In 21 patients with proven metastatic disease serial imaging studies were performed. HPI was determined using the peak of the left kidney time-activity curve to define the division of arterial and portal blood flow. HPI was elevated (greater than 0.37) in 54 of 115 patients (47%) with no evidence of hepatic metastases, 17 of 27 patients (63%) with hepatic metastases at initial presentation and 21 of 25 (84%) with metastatic disease detected during follow-up. Only 4 of 13 patients (31%) with local recurrence but no evidence of liver metastases had an elevated HPI. Serial imaging of patients with metastatic liver disease demonstrated a rising HPI with clinical disease progression in 18 of 21 patients (86%). This study confirms the association of an elevated HPI with hepatic metastases and suggests that a rising HPI in serial studies is associated with progression of disease but highlights the deficiency of one single HPI estimation in the identification of patients with overt hepatic metastases.

Colorectal Neoplasms↗
PubMed1990

Echinococcus granulosus: the potential use of specific radiolabelled antibodies in diagnosis by immunoscintigraphy.

Diagnosis of hydatid disease in man is frequently dependent on the imaging of cysts in situ by techniques such as ultrasonography and CAT scans. Such methods are useful but are not specific and can lead to errors in diagnosis. The present work reports preliminary experiments on the development of a specific imaging technique for hydatid cysts using radiolabelled antibodies. A purified preparation of antigen B of hydatid fluid was used to raise polyclonal antisera in rabbits and the resulting affinity-purified IgG labelled with 131I. Gerbils with an established Echinococcus granulosus infection were injected intraperitoneally with the labelled antibody and imaged 48 h later with a gamma camera. Hydatid cysts could be identified within the peritoneal cavity and post-mortem assessment of activity showed the cysts to contain approximately four times as much activity as the surrounding organs thereby indicating successful targeting of the antibody to the cysts.

Animals↗
PubMed1989

111In-labelled leucocyte imaging in vascular graft infection.

Twelve patients with a clinical diagnosis of possible vascular graft infection have been studied over the last 3 years. All patients had their leucocytes labelled with indium-111 and gamma-camera imaging after 24 and 48 h. Subsequent management was according to established surgical techniques. Eight patients proved to have vascular graft infection and indium uptake was seen along the length of the graft in six. Two patients with open wound infections and synthetic grafts had localized uptake only on leucocyte scanning. Four patients, all of whom had negative scans were not thought to have infected grafts after further investigation using digital subtraction angiography and computed tomography scanning. These patients have been followed up for a median period of 19 months (range 5-25 months) and have remained symptom free. Initial experience with 111In-labelled leucocyte scanning has been encouraging, both in diagnosis and in planning the management of patients with graft infections.

Bacterial Infections↗
PubMed1989

A comparison between visual and quantitative analysis in a prospective evaluation of labelled 111In leucocyte imaging in vascular infection.

In a continuing evaluation of 111In-oxine labelled leucocyte imaging in vascular surgery, we have studied 16 patients with a clinical diagnosis of possible vascular graft infection. We have evaluated both visual and semi-quantitative analysis of the images obtained and have interpreted these in the light of the subsequent clinical outcome. Full length or multifocal uptake was seen in six patients, all of whom eventually required graft excision with two limbs surviving, and one death. These patients had a significantly higher uptake ratio (median = 3.26) than those with either localized (median = 1.12; p = 0.0027) or negative images (median = 0.72; p = 0.0003). Of four patients showing localized uptake only, one required amputation for continuing sepsis. Six patients had negative images, and had normal DSA and CT scans. Uptake ratios could not distinguish between those with localized images and those with negative images. Computer generated vertical profiles aided separation of patients with presumed localized and negative images. Semi-quantitative analysis has proved to be a reliable method which should allow a more direct comparison of the efficacy of various investigative techniques and of the results of therapy, independent of intra-observer subjective bias.

Aged↗
PubMed1989

Intraperitoneal 131I- and 111In-791T/36 monoclonal antibody in recurrent ovarian cancer: imaging and biodistribution.

An examination of the biokinetics and biodistribution of i.p. administered 131I- or 111In-labelled 791T/36 antibody (1 mg) has been carried out in five patients with stage III/IV ovarian cancer. Blood kinetics and urinary excretion of the radiolabels were assayed. Scintigraphy was performed immediately following administration and before and after peritoneal lavage at 48 h. Blood levels of both preparations rose over the first 20-40 h reaching 8-14% of the administered dose in the circulation and then declined (T1/2 of 40 h). Circulating radiolabel was still attached partially to antibody as shown by precipitation with anti-mouse IgG antiserum. The rapid appearance of radiolabel in the bloodstream meant that any tumour localization could be from circulating antibody rather than local infiltration. Interpretation of the images was difficult and the distribution of the tracer was different from that previously observed using i.v. administration of antibody. In some cases the images were confusing and the uptake of activity did not fit in with the clinical knowledge of the disease or the findings from laparoscopy. Tumour specimens resected at 4-5 days showed up to 0.02% of the dose g-1.

Adult↗
PubMed1989

Immune hemolysis after an ABO mismatched renal transplant.

We describe a case of immune hemolysis due to anti-B occurring in a blood group B patient 16 days after a cadaveric renal transplantation from a blood group O donor. Transfusional support was initially required and the direct antiglobulin test (DAT) remained positive for 80 days. Cyclosporin A (CSA), which was used for rejection prophylaxis in this case, has unique immunosuppressive capabilities which protects transplanted organs from rejection, but which might permit this type of 'graft versus host' reaction.

ABO Blood-Group System↗
PubMed1988

Fulminant postsplenectomy sepsis.

The vital role of a normally-functioning spleen in a host's defence against circulating microorganisms has been realized for many years. The fulminant clinical course that characterizes infection with encapsulated microorganisms in asplenic patients is highlighted in these cases of severe pneumococcal sepsis in two patients, 10 and 13 years after splenectomies for idiopathic thrombocytopenic purpura. Approaches to the acute management of septic episodes and preventive measures are discussed. Pneumococcal vaccination reduces the incidence of infection effectively in asplenic patients and has a low complication rate. Penicillin by mouth is also efficacious in this situation, but patient compliance is low. Our current practice is to offer pneumococcal vaccination to all patients who have undergone splenectomy in the past and to administer the vaccine two weeks before elective splenectomies. Asplenic patients should be educated about the potential dangers of a septic episode and should be urged to seek an early medical consultation when this occurs.

Acute Disease↗
PubMed1988

Biodistribution of a monoclonal antibody-methotrexate conjugate (791T/36-MTX) in patients with colorectal cancer.

The monoclonal antibody (MAb) 791T/36 which has previously been shown to localise in colorectal cancer has been conjugated to methotrexate (MTX) for potential use as a chemotherapeutic agent in malignant disease. To examine its biodistribution and tumour localisation, 16 patients with primary colorectal cancer were injected intravenously with 131I-labelled 791T/36-MTX conjugate and imaged using a gamma camera after 48-72 hr. Serial blood samples were taken to determine the levels of circulating conjugate and samples of tumour and normal colon were assayed for uptake of radioactivity. Whole body biodistribution, visualised by gamma scintigraphy, and blood clearance of both the antibody and drug moieties of 791T/36-MTX were similar to that previously found with unconjugated antibody. Assays of tissue radioactivity showed positive tumour uptake of drug-antibody conjugate (T:NT greater than 1.9:1) in 13/15 primary tumour specimens (median T:NT = 2.9:1). These studies indicate that 791T/36-MTX conjugates may have potential in the treatment of metastatic colorectal carcinoma.

Aged↗
PubMed1988

A rat model for imaging the effect of anti mouse antibody responses on the biodistribution of radiolabelled mouse monoclonal antibodies.

Rats were injected both intradermally and intravenously with an IgG2b mouse monoclonal antibody (791T/36) and subsequently the biodistribution of intravenously injected 111In labelled antibody was examined by gamma camera imaging in these and control rats. The majority of pretreated rats showed a marked perturbation of the biodistribution of the radiolabelled antibody with a marked increase of the tracer in the liver. There was similar perturbation of the biodistribution of subsequently administered 111In labelled Fab fragment of the 791T/36 antibody and of another IgG2b monoclonal antibody. In contrast, there was little influence on the biodistribution of IgG2a or IgG1 monoclonal antibodies, indicating that the response in the rats was predominantly against the IgG2b isotype. This rat model system is amenable to examination of a number of aspects of the biological consequences of immune responses to foreign immunoglobulins relevant to their use for clinical imaging.

Animals↗
PubMed1988

Gamma camera emission tomography using radiolabelled antibodies.

Single photon emission computed tomography (SPECT) of 52 patients injected with 131I and 111In labelled monoclonal antibodies has been undertaken. Patients with tumours within the thorax or lower abdomen were imaged 48-72 h following administration of 80 MBq 131I or 111In labelled monoclonal antibody. Tumour detection from the reconstructed views was compared with that from the planar images. Studies of patients injected with 131I labelled antibodies required long data collection times otherwise image quality was unsatisfactory. Emission tomography using 111In labelled antibodies provided high quality reconstructed images using data collection times acceptable for most patients, and tumour deposits not confidently detected on planar images were clearly visualised in the axial views. These studies demonstrate the potential of radiolabelled antibody emission tomography.

Antibodies, Monoclonal↗
PubMed1988

A comparison of iodine and indium labelled anti CEA intact antibody, F(ab)2 and Fab fragments by imaging tumour xenografts.

An intact anti CEA monoclonal antibody (C198) and its F(ab)2 and Fab fragments have been radiolabelled with 131I and 111In and their biodistributions and tumour imaging capabilities examined in mice with human tumour xenografts. 131I labelled F(ab)2 and Fab fragments showed improved tumour visualization compared with intact antibody, principally because of the more rapid whole body elimination of the radiolabel. Studies using 111In labelled fragments demonstrated that a major proportion (greater than 60%) of the administered radioactivity was retained in the kidneys and this was detrimental to tumour imaging in the mouse xenograft model. The present study emphasizes the importance of selecting the most appropriate combination of antibody preparation and radiolabel, and that the choice of radionuclide is influenced by both its physical and subsequent pharmacological characteristics.

Animals↗
PubMed1988

Iodine-131 and indium-111 labelled avidin and streptavidin for pre-targetted immunoscintigraphy with biotinylated anti-tumour monoclonal antibody.

Studies have been carried out in mice to examine by gamma camera imaging and dissection analysis the biodistribution of 131I- and 111In-labelled avidin and streptavidin. This has included mice with human tumour xenografts pre-targetted with biotinylated anti-tumour monoclonal antibody. Both iodine-labelled avidin and streptavidin were cleared rapidly from the circulation particularly to kidneys, which showed prolonged retention of the tracer. Similar distribution was seen with 111In-labelled preparations, although here tracer also accumulated in the liver. Radiolabelled preparations could form complexes in vitro with a biotinylated monoclonal antibody. This biotinylated antibody, following radioiodine labelling, localized in xenografts of a human osteosarcoma. When xenografted mice were injected with biotinylated antibody followed by 111In-labelled avidin, levels of tracer per gram of tumour tissue were four times higher than those in non-pretreated mice. However, there was still marked liver and kidney uptake of tracer and, since this dominated the images, tumours were not visualized by scintigraphy.

Animals↗