Choice of imaging agent in inflammation.
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Antibodies↗
Biomedical subjects
A C Perkins
Publications and source records attributed to A C Perkins.
Intra-operative nuclear medicine in surgical practice.
The use of radionuclides for the intra-operative localization of tumours has increased steadily over the past 15 years. We reviewed more than 15 years experience of a peripatetic service using a sterilizable probe system in operating theatres throughout the UK for localizing bone and soft tissue lesions. The technique requires the positive concentration of an appropriate radiopharmaceutical, together with a suitably designed detector system which can be sterilized for use during surgery. All surgical procedures were undertaken following initial positive imaging studies. A well-collimated nuclear probe with a 5 mm diameter CdTe detector was sterilized with ethylene oxide gas and coupled to a digital counter and ratemeter for use in the operating theatre. A total of 68 surgical procedures have been undertaken at 35 hospitals. Fifty-eight patients underwent excision of osteoid osteoma subsequently proven by histology. The other lesions successfully resected included osteoblastoma, hamartoma, Brodie's abscess, chronic bone infection, ectopic parathyroid adenoma and metastatic neuroblastoma. The technique can now be regarded as the method of choice for the surgical localization of osteoid osteoma. The successful detection of lesions at surgery can be assured providing that clear localization of the radiopharmaceutical occurs on the pre-operative images. The intra-operative use of conventional and new tumour-specific radiopharmaceuticals is reviewed and we confirm an increasing role for the surgical-probe-guided localization of primary and metastatic tumours.
Adenoma↗
Lymphoscintigraphy and colour Doppler sonography in the assessment of leg oedema of unknown cause.
Oedema of the lower limbs may be associated with a number of factors, most commonly a lymphatic or venous abnormality. Generally effective treatment options are only available with venous disorders. The aim of this study is to show that a combination of duplex Doppler sonography and lymphoscintigraphy in patients with limb oedema will help to determine the aetiology and thus identify patients for whom treatment is appropriate. 32 patients presenting with unexplained oedema involving the lower limb have been studied. Each patient underwent Doppler sonography followed by lymphoscintigraphy. In 16 patients the lymphoscintigraphy was abnormal, showing absent or poorly visualized lymphatics. The Doppler study was abnormal in 17 patients, nine of whom went on to receive definitive surgical treatment. In five patients both studies were abnormal and there were six cases where both investigations were normal. It is concluded that in the great majority of referrals (82%), the combination of lymphoscintigraphy and Doppler ultrasound is a satisfactory means of assessment of patients with unexplained limb oedema.
Adolescent↗
Gamma scintigraphy of the biodistribution of 123I-labelled N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugates in mice with transplanted melanoma and mammary carcinoma.
An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin conjugate is currently under clinical evaluation as a new antitumour agent. It has been shown previously that such conjugates exhibit selective tumour accumulation. In this study HPMA copolymer doxorubicin conjugates of low (LMW) or high (HMW) molecular weight were synthesised (which had a weight average molecular weight (Mw) of 25,000 and 94,000 respectively) and additionally contained a small amount (1 mol%) of the comonomer methacryloyltyrosinamide to permit labelling with [123I or 125I]iodide. Gamma camera imaging using the 123I-labelled probes was used to follow time-dependent biodistribution after intraperitoneal (i.p.) or intravenous (i.v.) administration to mice bearing subcutaneously either B16F10 melanoma or a mammary carcinoma. Imaging showed more rapid clearance of LMW conjugate from the peritoneal cavity than HMW conjugate. The images of mice given the LMW conjugate revealed rapid urinary excretion of radioactivity after both i.p. and i.v. injection with an early high concentration of tracer in the bladder, and subsequently a very high concentration in the kidneys, which came to dominate the views. Dissection analysis 2 days after administration of the LMW conjugate revealed a kidney level of radioactivity corresponding to 25-40% dose/g tissue in mice bearing the two tumour models. Following administration of the HMW conjugate kidney accumulation at 2 days was less due to retention of the higher molecular weight polymer molecules in the circulation, and spleen and liver displayed the highest concentrations of radioactivity. The tumour accumulation of LMW and HMW conjugates was; mammary carcinoma 3.18 and 5.29% dose/g respectively; B16F10 melanoma 3.23 and 8.82 %dose/g although these levels of tracer enabled visualisation in the images of the mammary carcinoma with HMW conjugate at later time points. The smaller size of the B16F10 tumour masses did not permit clear visualisation.
Animals↗
Gamma scintigraphy of a 123I-labelled N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin conjugate containing galactosamine following intravenous administration to nude mice bearing hepatic human colon carcinoma.
Polymer drug conjugates composed of N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer covalently bound doxorubicin, and containing additionally galactosamine to facilitate hepatocyte-specific targeting (HPMA copolymer-dox-gal), were synthesised to contain a small amount (approximately 1 mol%) of the monomer methacryloyltyrosinamide to permit radioiodination with [123I]iodide. After intravenous administration to both normal mice and nude mice bearing hepatic human colon carcinoma, the biodistribution of the conjugate was monitored using the gamma camera, and also by dissection analysis. Efficient liver accumulation of HPMA copolymer-dox-gal was seen in the gamma camera images within 20 min, both in normal and tumour-bearing animals. Quantitatively liver uptake was approximately 40% dose administered/g liver. Images of the tumour-bearing animals showed clearly a much lower accumulation of HPMA copolymer-dox-gal in the colon carcinoma deposits within the liver (3-9% dose/g tumour), and this lack of uptake was verified by ex vivo imaging of the tumour-containing liver and also by dissection analysis. It can be concluded that 123I-labelled HPMA copolymer conjugates offer great potential as effective imaging agents and can be used for future non-invasive clinical studies. This nuclear imaging method will enable optimisation of the dosing schedule by identification of doses of HPMA copolymer-dox-gal that display receptor saturation (and hence diminished targeting efficiency). In addition this conjugate can provide negative images of liver-associated tumour deposits that do not express the asialoglycoprotein receptor.
Animals↗
Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF.
Globin genes are regulated in a tissue-specific and developmental stage-specific manner, with the beta-globin gene being the last to be activated in the beta-gene cluster. CACCC-nucleotide sequences, which bind multiple nuclear proteins, including ubiquitously expressed Sp1 and erythroid Krüppel-like factor (EKLF), are among the cis-regulatory sequences critical for transcription of globin and non-globin erythroid-expressed genes. To determine the function of EKLF in vivo, we created mice deficient in EKLF by gene targeting. These embryos die of anaemia during fetal liver erythropoiesis and show the molecular and haematological features of beta-globin deficiency, found in beta-thalassaemia. Although it is expressed at all stages, EKLF is not required for yolk sac erythropoiesis, erythroid commitment or expression of other potential target genes. Its stage-specific and beta-globin-gene-specific requirement suggests that EKLF may facilitate completion of the fetal-to-adult (haemoglobin gamma to beta) switch in humans.
Anemia↗
Three-dimensional visualisation of the large bowel: a potential tool for assessing targeted drug delivery and colonic pathology.
A study has been undertaken to assess the feasibility of three-dimensional imaging of the dispersion of a non-absorbable tracer released into the colon of normal subjects. Six healthy volunteers were selected who were participating in a scintigraphic study designed to assess the spreading of 1 MBq indium-111 Amberlite resin delivered from a delayed capsule system targeted to release in the ascending colon. In each case subjects were imaged using a rotating gamma camera over a data collection period of approximately 20 min. Three-dimensional volume rendered images demonstrated good visualisation of the dispersion of the tracer throughout the ascending, transverse and descending colon and provided good anatomical visualisation of the shape of the colon, not previously apparent from the planar views. The present study demonstrates for the first time, the successful three-dimensional imaging of a radiolabelled tracer dispersed throughout the colon and opens up the prospects for more detailed study of quantification of the volume and distribution of tracers contained within the colon.
Adult↗
Tissue retention of indium-labelled antibodies.
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Humans↗
Gamma scintigraphy of 111In-labelled branched chain polypeptides (BCP) with a poly(L-lysine) backbone in mice with mammary carcinoma: effect of charge on biodistribution and tumour imaging potential.
Radiolabelled synthetic branched chain polypeptides (BCP) represent a new and novel range of materials with potential as radiopharmaceuticals. Preliminary imaging studies have been undertaken with 111In-labelled BCP in mice with subcutaneously transplanted mammary carcinoma. Four polypeptides each with a poly(L-lysine) backbone and side chains of DL-alanine residues were studied. These were AK, which is polycationic, EAK which is amphoteric, having additional glutamic acid residues at the end of the side chains, and AcEAK (anionic) and SucEAK (highly polyanionic) where the terminal glutamic acid amino groups were acetylated or succinylated respectively. Radiolabelling was achieved by previous conjugation with DTPA. Serial images up to 48 hours showed marked retention of 111In-labelled polycationic AK and polyanionic SucEAK in the liver and spleen, with renal uptake also being visible in the case of AK. 111In-labelled EAK and AcEAK showed longer blood survival with some liver uptake, but tumour uptake was also visualized by 24 hours with both of these polypeptides. These studies demonstrate the feasibility of using 111In-labelled synthetic branched chain polypeptides as radiopharmaceuticals for gamma scintigraphy and the visualization of tumours by modification of the side chain structure. These materials warrant further study.
Animals↗
A reproducibility study of technetium-99m macroaggregated albumin foot perfusion imaging in patients with diabetes mellitus.
The reproducibility of Technetium-99m macroaggregated albumin (99mTc-MAA) foot perfusion imaging was assessed in 14 diabetic patients with foot ulcers. Bilateral femoral intra-arterial injections of 99mTc-MAA were administered and the feet imaged with a gamma camera. Patients returned 1 week later for a repeat study. The scans of 10 patients including one unilateral amputee were evaluated. Of these 19 limbs there were 4 failed injections (21%). The remaining 15 completed repeat studies were analysed both subjectively and semiquantitatively by 2 different observers who were blind to the patient's name and scan date. Subjectively the images of each individual were similar with reports highlighting the same abnormalities. Semiquantitatively areas of increased uptake on both images were significantly correlated for each individual (Pearson's Rho correlation coefficient = 0.96, r2 = 0.92, p < 0.0001) as were areas of poor uptake reported, reflecting decreased tissue perfusion (Pearson's Rho = 0.93, r2 = 0.86, p < 0.0001). There were no side-effects. 99mTc-MAA has proven to be a safe, generally acceptable, and reproducible technique for assessing tissue perfusion in the extremities which provides an accurate means of differentiating viable from non-viable tissue in patients with foot ulcers.
Aged↗
Effect of a test meal on the intragastric distribution of urea in the 13C-urea breath test for Helicobacter pylori.
Test meals are invariably used in the 13C-urea breath test (UBT) but their effect on the intragastric distribution and gastric residence time of urea given in the test is unknown. The site of Helicobacter pylori urease measured in the test is unknown and whether the test measures total or regional gastric urease is uncertain. This study reports the results of paired UBTs with simultaneous gastric distribution studies, one with and one without a fatty test meal, two weeks apart on seven H pylori infected subjects. The test meal did not affect UBT results at 10 minutes, but increased values at 30 minutes and thereafter. The amount of scintigraphic label in the antrum at 10 minutes was also unaffected by the meal but increased at 30 minutes and thereafter, whereas the amount in the body/fundus was greatly increased both at 10 minutes and throughout the test. There was considerable variation in intragastric distribution of urea between subjects, both with and without the test meal. This study shows that a test meal profoundly affects intragastric distribution of urea solution in the UBT, and increases UBT values at 30 minutes and later. Variability between subjects, however, means that accurate measurement of total or regional gastric urease is probably unrealistic.
Adult↗
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↗
Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol.
A prospective placebo-controlled, randomized double-blind study of Acamprosate at two dose levels in alcohol-dependent patients followed up for 12 months was performed. After detoxification, each of the 538 patients included was randomly assigned to one of three groups: 177 patients received placebo, 188 received Acamprosate at 1.3 g/day (low dose group) and 173 received 2.0 g/day (high dose group) for 12 months. This was followed by a single blind 6 month period on placebo. The patients' mean age was 43.2 +/- 8.6 years. Their mean daily alcohol intake was high (nearly 200 g/day) and of long duration (9.5 +/- 7.1 years). Abstinence figures followed the order high dose > low dose > placebo. The difference was significant at 6 months (P < or = 0.02) but not at 12 months (P = 0.096). The number of days of continuous abstinence after detoxification was 153 +/- 197 for the high-dose group versus 102 +/- 165 for the placebo group (P = 0.005), with the lose-dose group reporting 135 +/- 189 days. Clinic attendance was significantly better in the Acamprosate groups than in the placebo group at 6 months (P = 0.002) and 12 months (P = 0.005). During the 6-month post-treatment period, no increased relapse rate or residual drug effect was observed. The side effect profile for Acamprosate was good compared with controls with only diarrhoea being reported more frequently (P < 0.01). This study confirms the pharmacological efficacy of Acamprosate and its good acceptability. As an adjunct to psychotherapy, this study supports the inclusion of Acamprosate in a strategy for treating alcoholism.
Acamprosate↗
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↗
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↗
A simple simulation for the visualisation of CSF flow in infants with hydrocephalus.
Cerebrospinal fluid (CSF) flow was demonstrated incidentally in our unit during the routine cranial colour Doppler examination of infants with hydrocephalus. Pulsed Doppler analysis of the flow jets within CSF has shown that for each CSF flow jet there is a characteristic sinusoidal wave pattern that decreases in amplitude at the end of each jet episode. Any activity that transiently elevates the intracranial pressure, such as crying, increased the intensity of this signal. A study was subsequently carried out to investigate the origin of these clinical observations of CSF flow. Using a simple flow phantom, experiments with degassed water demonstrated the transient production of a Doppler signal at a stenosis in an otherwise uniform bore tube. We postulate that in infants with obstructive hydrocephalus, high CSF velocities in excess of 25 cm/s are produced as a result of the pressure caused by the excess cerebrospinal fluid. In some instances fluid jets may give rise to the production of microbubbles that act as transient but extremely efficient reflectors for the ultrasound, thus enabling the visualisation of CSF flow in these patients.
Cerebrospinal Fluid↗
A perfusion phantom for the evaluation of ultrasound contrast agents.
A renal dialysis cartridge was adapted for use as a perfusion phantom for the investigation of ultrasound contrast agents. In preliminary studies using this phantom, it was possible to visualise the effects of introduction of contrast material into the system, on both real-time and colour Doppler imaging. It was also possible to make quantitative measurements relating to the backscatter and attenuation properties of the contrast material. The method of adapting the dialysis cartridge is economical and convenient, and should provide a useful in vitro model in which to evaluate and compare ultrasound contrast agents.
Contrast Media↗
Planar, SPET and three-dimensional immunoscintigraphy of suspected recurrent colorectal cancer using 111In-B72.3 (Oncoscint CR-OV): effect of administered activity.
The monoclonal antibody conjugate 111In-B72.3 was the first such antibody-based radiopharmaceutical for tumour detection to be granted a propriety product licence in Europe. However, the optimum activity of 111In for planar and SPET imaging is yet to be established. A baseline study of 20 patients with suspected recurrent colorectal cancer has been carried out to assess any effect of administered activity of radionuclide on image quality and tumour detection. Ten patients were administered 80 MBq 111In-Oncoscint and 10 patients a larger amount of activity, 150 MBq (resulting in effective dose equivalents of 25 and 47 mSv, respectively). Planar, orthogonal SPET and 3D volume-rendered SPET images were obtained and the image quality was assessed. The clinical results were compared with computed tomography (CT) and in selected patients magnetic resonance imaging (MRI). No difference in the overall tumour detection was apparent between the two groups and the use of 150 MBq 111In for planar imaging alone cannot be justified. Orthogonal and 3D SPET imaging was helpful in confirming sites of uptake and may justify the use of the higher administered amount of activity; however, false-positive results raise the need for caution in the interpretation of these images. Volume-rendered 3D images offer an attractive method of displaying antibody data and require further evaluation.
Aged↗