Radioimmunodetection of gastrointestinal neoplasms with antibodies to carcinoembryonic antigen.

Primary and secondary gastrointestinal tumors have been identified using sheep immunoglobulin G antibody to carcinoembryonic antigen radiolabeled with 131I. 99mTc-pertechnetate and 99mTc-human serum albumin were used to identify tissue spaces and blood pool and to facilitate external substraction imaging. In 13 patients with tumors, 4 of 5 primary sites and 8 of 11 secondary sites were successfully demonstrated. Two patients with benign disease had negative scans. Comparison with conventional methods of scanning showed good correlation.

Platelet inhibitory drugs: an in vivo method of evaluation in patients.

The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indium-labelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamole (ASA + DPM) or placebo. Autologous platelets were labelled and re-injected seven days following surgery and the graft thrombogenicity index calculated as the daily rise in the ratio of emissions from the graft over a reference site. The mean (+/- SD) thrombogenicity index in 12 patients undergoing femoro-popliteal bypass was 0.25 +/- 0.09 on placebo and 0.16 +/- 0.07 on ASA + DPM started pre-operatively (p less than 0.05). Post-operative ASA + DPM therapy started two days following platelet labelling in 15 patients with aorto-femoral grafts also significantly reduce thrombogenicity to 0.12 +/- 0.05 compared with 0.25 +/- 0.08 on placebo (p less than 0.01). In the latter patients the ratio of emissions from the graft over reference fell significantly on starting ASA + DPM, suggesting a net loss of platelets from the graft. These results indicate that the rate of in vivo platelet accumulation on Dacron grafts can be quantitated and that ASA + DPM reduced this rate in man.

Dacron arterial grafts: the influence of porosity, velour, and maturity on thrombogenicity.

It has been claimed that the neointimal healing of Dacron arterial prostheses can be enhanced by increasing porosity and including both an internal and an external velour layer. To test this, 24 patients received at random either woven (USCI, DeBakey, C. R. Bard, Inc.) or more porous, double-velour, knitted (Microvel, Meadox Medicals, Inc.) Dacron aortobifemoral prostheses. Graft thrombogenicity was measured using autogenous 111In-labeled platelets shortly following surgery and 6 to 9 months later. The thrombogenicity index was defined as the mean daily rise in the ratio of emissions over the graft to emissions over a reference area (aortic arch) and is a measure of platelet deposition. At early study the mean (+/- SE) thrombogenicity index was similar in woven and knitted graft patients at 0.19 +/- 0.4 and 0.14 +/- 0.2, respectively. In both groups it was lower (P less than 0.05) 6 to 9 months later at 0.06 +/- 0.2 (woven( and 0.08 +/- 0.1 (knitted), with again no difference between materials. Although platelet survival was restored to near normal values in both groups by 6 to 9 months, only one woven graft failed to demonstrate continued platelet accumulation by gamma-imaging. Thrombogenicity in Dacron grafts diminishes in the early months of maturation but is not affected by porosity and velour. Moreover, this thrombogenicity persists beyond the period of altered platelet survival.

Labelled antibody imaging in pancreatic cancer, cholangiocarcinoma, chronic pancreatitis and sclerosing cholangitis.

Pancreatic and biliary carcinomas are difficult to differentiate clinically from their benign counterparts, chronic pancreatitis and sclerosing cholangitis. Immunohistochemical differences in CEA expression have previously been demonstrated in these conditions. We have therefore investigated the use of a monoclonal anti-CEA antibody (11-285-14) in distinguishing between these conditions in vivo. Twenty-five patients with these four conditions underwent radioimmunolocalisation studies. Diagnosis was confirmed by laparotomy and biopsy (n = 21), CT scanning (n = 1) or ERCP (n = 3). Positive images were obtained in 11/12 pancreatic cancers and 2/3 biliary tumours. However, 4/8 cases of chronic pancreatitis and 1/2 cases of sclerosing cholangitis also had positive images. This high false positive rate suggests that antibody imaging is unable to differentiate reliably between benign and malignant pancreatico-biliary conditions.

Evaluation of bile duct complications after orthotopic liver transplantation by hepatobiliary scanning.

A new radiopharmaceutical for hepatobiliary scanning, 99Tcm Iodida, which has significant advantages in patients with high bilirubinaemia, was used to assess biliary tract complications in 30 consecutive liver transplant patients. There was adequate hepatic extraction and excretion for diagnostic imaging even in patients with serum bilirubin levels up to 877 mumol l-1 (51.6 mg dl-1). Twelve out of 12 cases (100%) without any biliary complication were correctly diagnosed. Extrahepatic obstruction was recognized in 5 out of 7 cases (71%). In one case the scintigraphic findings showed no perfusion of the transplanted liver caused by vascular thrombosis due to acute rejection. One small biliary leak was missed. The correct diagnosis of intrahepatic cholestasis was made in 3 out of 9 patients. However six equivocal studies were observed in profoundly jaundiced patients with bilirubin levels above 400 mumol l-1 due to difficulties in differentiating extrahepatic obstruction from severe intrahepatic cholestasis. Quantitative analysis of the kinetics of 99Tcm Iodida may permit better discrimination between the wide variety of disease in the posttransplant period.

Assessment of the defunctioning efficiency of the loop ileostomy.

The defunctioning efficiency of the loop ileostomy has been assessed using a radioisotope and dye technique. The median defunctioning capacity in patients without episodes of fecal discharge per rectum (n = 18) was 99.99 percent and was not affected by body position or the formation of a dependent stoma. In patients (n = 4) who passed fecal material per rectum but who had no stomal retraction, the median defunctioning efficiency was 99.99 percent, and continued fecal discharge was considered to be due to mucopurulent secretion from active distal disease. In patients who passed fecal material per rectum and also had a retracted stoma (n = 4), the defunctioning efficiency was significantly reduced (median = 84.70 [31.2-99.10 percent; P less than 0.01]), owing to the overspill into the distal limb. Two patients underwent stomal revision, with an improvement in defunctioning efficiency to 99.99 percent.

Long-term follow-up of treatment of thyrotoxicosis by three different methods.

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long-term outcome of radioiodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half-life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110, 185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10-year follow-up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5%. At 5 years, 18% were hypothyroid, the prevalence rising to 42% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7%. The rate of hypothyroidism at 5 years (38.5%) was higher than that found in the calculated dose group. A minimum 10-year follow-up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2%. The prevalence of hypothyroidism (2% at 5 years, 27.5% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet accumulation on mature Dacron grafts in man.

Prosthetic graft occlusion is most frequent in the early postoperative period when the luminal surface is highly thrombogenic. It is generally believed that graft maturation ultimately results in a non-thrombogenic surface. The accumulation of 111-indium-labelled autologous platelets in Dacron aortofemoral grafts has been measured 1 week following surgery and at intervals of 6 months to 1 year. Platelets from 9 patients were labelled with 111-indium oxine and re-injected. Isotope emissions over the graft and a reference site (aortic arch) were measured daily for 8 days and gamma camera images taken on alternate days. Graft thrombogenicity was calculated as the daily rise in the graft: reference ratio of emissions. All grafts, regardless of age, accumulated platelets and were imaged by gamma camera. Mean thrombogenicity (+/- s.e.mean) 1 week after surgery was 0.21 +/- 0.04 compared with 0.08 +/- 0.03 at follow-up (P less than 0.01). The platelet survival during the early study was reduced at 6.8 +/- 0.6 days but recovered to a value of 8.6 +/- 0.8 days (P less than 0.01) at follow-up. Further grafts, 2, 5 and 9 years old, were studied and all accumulated platelets, especially near the anastomoses. Platelet accumulation on Dacron grafts does diminish with time but persists beyond the period of altered platelet survival and perhaps indefinitely.

In vivo and in vitro precision for bone density measured by dual-energy X-ray absorption.

An investigation was made into some of the major sources of error influencing the bone mineral density (BMD) measurements of the lumbar vertebrae, the femoral neck and the greater trochanter. The effect on accuracy and reproducibility of the following parameters was investigated: influence of patient positioning, patient size, scan speed, the technique of scan analysis and the temporal variation in instrument performance. The in vitro precision, both long-term and short-term, was assessed using aluminium phantoms supplied by the manufacturer. For the spine phantom, the precision expressed as a percentage coefficient of variation (%CV) was found to be 0.4% (10 scans) in the short term and 0.55% (15 scans) in the long term. Measured precision (short-term) for the three regions of the femur phantom analysed by the software was 1.3% for the neck of femur, 1.7% for Ward's triangle and 0.6% for the trochanter. Long-term precision was 1.0%, 1.9% and 1.1% respectively. No statistically significant difference was found between long- and short-term results. Short-term in vitro precision on a low density anthropological phantom was 4.1%, 4.2%, 2.4% and 0.61% for neck of femur, Ward's triangle, trochanter and spine respectively. In vivo short-term precision for the lumbar spine (L2-L4), measured by scanning four normal volunteers five times in one session, was found to be 0.8 +/- 0.25%. In vivo precision for the femur, measured on seven volunteers was 1.6 +/- 0.8% for the neck of femur, 3.2 +/- 1.7% for Ward's triangle and 2.2 +/- 1.1% for the trochanter.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison and investigation of bone mineral density in opposing femora by dual-energy X-ray absorptiometry.

A dual-energy X-ray absorptiometry (DXA) machine was used to measure the bone mineral density (BMD) of both femora in 760 female volunteers. Each volunteer completed a questionnaire and exclusion criteria were applied such that only 480 of these were considered normal subjects. The remaining 280 women failed to comply with the criteria and were considered 'abnormal'; their BMD results were analysed separately. Two abnormal subgroups, one with previous long bone fractures and one with radiologically diagnosed osteopenia, were studied. BMD values for femoral neck, Ward's triangle and trochanter were compared between the two femora in all the above groups. No dominance relationship was found when comparing left to right femur, averaged over any population studied, but large differences were found between the femora in individual volunteers. There was a high correlation between BMD in opposing femora of 0.91, 0.91 and 0.84 for the femoral neck, Ward's triangle and trochanter respectively. However, in normal subjects the percentage variation in these regions ranged up to 34%, 64% and 80% respectively at the different femoral sites. In addition, the normal population was divided into two subgroups, one in which the density difference between the femora was large, and the other in which the difference was statistically insignificant. The analytical and anatomical variations between these two groups were investigated. Only part of the difference appeared to be due to analytical problems and it seems that there is a genuine difference in femoral density. Poor correlation for femoral neck percentage density difference was found with average BMD, age, height and weight in the normal population.(ABSTRACT TRUNCATED AT 250 WORDS)

Indium leucocyte imaging in true pyrexia of unknown origin.

A patient with pyrexia of unknown origin (PUO) was investigated for a focal infection using autologous indium-labelled leucocytes. Only one site of increased activity was observed; this was asymptomatic and subsequently proved to be an infected nasal sinus. This case highlights the necessity, in PUO investigations, of carrying out whole-body imaging rather than just investigating the areas with presenting symptoms.

Imaging of 111In-labelled platelets--a new method for the diagnosis of deep vein thrombosis.

A radionuclide method for detecting established thrombi at all sites in the lower limb would have several advantages. Autologous platelets were labelled with 150 microCi (5.5 MBq) indium-111-oxine and re-injected into patients who were imaged with a gamma camera and data processed by a medical computer. Areas of increased uptake on imaging were correlated with the sites of thrombi identified by bilateral ascending venography. Venography in 27 patients identified 12 unilateral and 5 bilateral thrombi. On the day following the re-injection of labelled platelets, imaging identified thrombi at 13 sites in 24 limbs giving an overall correlation with venography of 84.4 per cent, correlation for the calf and thigh being 79.5 per cent and 89.1 per cent respectively. In the thigh 57.1 per cent of thrombi were identified by imaging and 52.9 per cent in the calf. Activity over thrombi was at least 20 per cent higher than in adjacent areas or at similar sites in the contralateral leg. Herapin therapy is considered to affect the detection of deep vein thrombus adversely by this technique. The technique offers a useful method for the diagnosis of both early and established thrombi at any site in the lower limb.

Indium-111-labelled leucocytes in the diagnosis of abdominal abscess.

The extensive morbidity and mortality of intra-abdominal abscess is mainly due to the delay in a diagnosis. The diagnostic accuracy of 111In-labelled mixed leucocytes with gamma imaging has been investigated in 100 consecutive patients including 34 following surgery and 36 with inflammatory bowel disease. White cell scans were performed 24 h following injection of autologous 111In-labelled leucocytes and were compared with clinical outcome where abscess was only diagnosed when pus either discharged or was drained at operation. Gamma images detected 28 of the 30 abscesses with no false positives giving 93 per cent sensitivity and 100 per cent specificity. Loculi of pus were identified in 11 of the 36 patients with inflammatory bowel disease with no errors in interpretation. Inflammation was reported in 15 of the remaining 25 patients with known but not necessarily active inflammatory bowel disease. 111In-labelled leucocyte imaging provides a rapid, safe and precise method for detecting intra-abdominal abscess even in the presence of inflammatory bowel disease.

Comparison of 51Cr-EDTA and 99mTc-DTPA slope clearances in children with vesicoureteric reflux.

The plasma clearances of 51Cr-EDTA and 99mTc-DTPA have been compared in a series of 154 children with reflux nephropathy. The study has shown that DTPA can replace EDTA with the advantage that it can also be used for dynamic renal imaging and calculation of individual kidney function. However, the source of the DTPA is important, as it has been shown to affect the comparison with EDTA clearance.

Liver scans in cystic fibrosis.

Liver scans were performed on 16 cystic fibrosis patients. Most scans were considered abnormal. In most patients, the results of serological liver function tests were normal. Liver scanning in cystic fibrosis is unlikely to make a significant contribution to an assessment of prognosis.

Femoropopliteal bypass grafts--an isotope technique allowing in vivo comparison of thrombogenicity.

Prosthetic femoropopliteal grafts attract platelet thrombus and often occlude in the months following implantation. Hence a technique to measure the in vivo thrombogenicity of different vascular substitutes in patients has been developed. In 28 patients the rate of accumulation of 111-indium-labelled platelets in saphenous vein, polytetrafluoroethylene (PTFE) and double velour Dacron femoropopliteal grafts was studied. One week postoperatively autologous 111In-labelled platelets were injected and the isotope emissions over the graft and contralateral leg counted. Graft thrombogenicity was calculated as the daily rise over 7 days in the ratio of counts over the graft to those over the contralateral leg. Mean thrombogenicity index (+/- s.e.mean) was greatest in the Dacron grafts at 0.24 +/- 0.03 which compared with 0.13 +/- 0.02 in PTFE (P less than 0.05). Saphenous vein was markedly less thrombogenic than either prosthetic graft with a mean index of only 0.025 +/- 0.01 (P less than 0.01). Platelet survival failed to differentiate the three graft materials, demonstrating that the direct measurement of 111In platelet deposition was a more sensitive technique.

111-Indium platelet imaging, Doppler spectral analysis and angiography compared in patients with transient cerebral ischaemia.

We have evaluated carotid gamma imaging using 111Indium-labelled platelets in the diagnosis of carotid artery disease and measured the accumulation of labelled platelets on endarterectomy specimens. Autologous 111In labelled platelets were injected in 25 patients with TIA. Gamma images were then taken daily and independently interpreted by two observers. Carotid endarterectomy was performed in 11 patients allowing measurement of the radioactivity on the operative specimen. These results were compared to the findings on angiography and Doppler spectral analysis. All endarterectomy specimens accumulated platelets with the most active equivalent to platelets from 1.8 ml blood. Atheromatous ulcers were more active than stenoses with mean (+/- SEM) activities of 1.12 +/- 0.37 and 0.38 +/- 0.10 respectively. These radioactivity levels were at the threshold of gamma camera resolution in a theoretical model. Both observers agreed that 22 of the 50 carotid bifurcations showed platelet accumulation on gamma imaging. Of the 12 atheromatous ulcers demonstrated by angiography 11 were visualized, but only five of ten stenoses greater than 80% were detected. As Doppler identified all stenoses only one angiographically diseased carotid was not detected by combining ultrasound with platelet scanning. Atherosclerotic arteries accumulate 111In platelets and the more thrombogenic ulcerated plaques are identified more frequently than stenoses. Long-term follow-up is required to establish the clinical relevance of platelet deposition.

Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning.

Biliary tract obstruction or anastomotic leakage are common problems following liver transplantation. In a sequential study, 31 patients with a liver transplant were investigated by 99mTc-IODIDA (IODIDA) scanning and T tube cholangiography (TTC) and the results were compared with clinical outcome. Seven patients had an extrahepatic biliary obstruction and one patient had a biliary leak. In the detection of biliary complications TTC and IODIDA scanning were similar in terms of sensitivity (63 per cent for both) but TTC had a better specificity (79 per cent versus 60 per cent) and accuracy (74 per cent versus 60 per cent) than IODIDA scanning. When liver function was taken into account, the diagnostic efficacy of both tests in patients with bilirubin levels of less than 200 mumol/l was similar. With levels greater than 200 mumol/l there was a greater number of false positive results with IODIDA scanning (12 per cent versus 54 per cent). The only significant biliary leak was clearly detected by TTC but not IODIDA scanning. TTC remains the more effective way of evaluating the biliary tract after transplantation. IODIDA scanning has limited value when bilirubin levels are elevated, but may provide additional information about blood supply, hepatocyte function and intrahepatic cholestasis.

Localisation of tumour deposits by external scanning after injection of radiolabelled anti-carcinoembryonic antigen.

Sheep IgG antibody to carcinoembryonic antigen (CEA) was radiolabelled with 131I and used to identify human gastrointestinal tumours by external subtraction imaging. 99Tc-pertechnetate and 99Tc-human serum albumin were used to identify tissue spaces. In 13 patients with tumours four out of five primary sites and eight out of 11 secondary sites were successfully shown. Two patients with benign disease had negative scans. Comparison with conventional methods of scanning showed good correlation. The success of this pilot study should encourage the search for more tumour-specific antigens and further study of the implications for treatment.