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Objective: Meta-iodo-benzyl-guanidine labelled with 131-iodine [(131)I-mIBG] has been used extensively for imaging tumours originating from the neural crest but experience with its therapeutic use is limited, particularly for non-catecholamine secreting tumours. In order to assess the therapeutic response and potential adverse effects of the therapeutic administration of (131)I-mIBG, we have reviewed all patients who had received this form of treatment in our department., Design: Retrospective analysis of the case notes of patients with neuroendocrine tumours who received treatment with (131)I-mIBG and were followed-up according to a defined protocol in a given time frame., Patients: Thirty-seven patients (18 with metastatic carcinoid tumours, 8 metastatic phaeochromocytoma, 7 metastatic paraganglioma and 4 metastatic medullary carcinoma of the thyroid) treated with (131)I-mIBG over a 15-year period were included in this analysis., Measurements: The symptomatic, hormonal and tumoural responses before and after (131)I-mIBG therapy over a median follow-up duration of 32 months (range 5-180 months) were recorded. Of the 37 patients (22 males; median age 51 years, range 18-81 years), 15 were treated with (131)I-mIBG alone whereas the other 22 received additional therapy., Results: A total of 116 therapeutic (131)I-mIBG doses were administered [mean cumulative dose 592 mCi (21.9 GBq); range 200-1592 mCi (7.4-58.9 GBq)]. None of the patients showed a complete tumour response. However, 82% of patients treated with (131)I-mIBG alone and 84% who received additional therapy showed stable disease over the period of follow-up. Overall survival during the period of the study was 71%. The overall 5-year survival rate was 85% (95% confidence interval, 72-99%) for all patients and 78% (95% confidence interval, 55-100%) for the carcinoid group alone, according to Kaplan-Meier analysis. Symptomatic control was achieved in all the patients treated with (131)I-mIBG alone, and in 72% of those receiving additional therapy. Hormonal control was noted in 50% and 57% of patients, respectively. (131)I-mIBG therapy was safe and well tolerated. Serious side-effects necessitating the termination of (131)I-mIBG therapy were seen in only 2 of our patients., Conclusions: (131)I-mIBG therapy produces symptomatic and hormonal improvement and moderate tumour regression/stabilization in patients with metastatic neuroendocrine tumours with minimal adverse effects. It may be a valuable alternative or additional therapeutic option to the currently available conventional treatment modalities.

Unlabelled: 99mTc-labeled ciprofloxacin (infecton) has been developed for detecting infectious foci, which localize in high concentrations in living bacteria. Other studies performed with various infections in animals and humans have found that infecton is a promising agent with better specificity for bacterial infections than white blood cell (WBC) scans. In this study, we evaluated the efficacy of infecton scintigraphy for detecting chronic bone and joint infections., Methods: Fifty-six sites with suspected bone or joint infection were examined with 99mTc-WBC and infecton scans in 51 patients. Of these patients, 21 had prosthetic implant materials. Biochemical, radiologic, and microbiologic data and clinical outcomes also contributed, along with the results from scintigraphic techniques, in determining the presence or absence of infection. Scintigraphic images were produced at 1 and 4 h after injection of 370-400 MBq infecton or 185-200 MBq 99mTc-hexamethylpropyleneamine oxime (HMPAO)-WBCs. For each patient, there were at least 2 d and at most 7 d between scintigraphic studies., Results: There were 30 true-positive, 4 false-positive, 20 true-negative, and 2 false-negative results with infecton. With 99mTc-HMPAO-WBCs, the results were 20, 1, 23, and 12, respectively. Values for sensitivity, specificity, and accuracy were 94%, 83%, and 89%, respectively, with the infecton scan and 63%, 96%, and 77%, respectively, with WBC scanning. Differences between the two agents were statistically significant (P < 0.001). Infecton and WBC scan results were in general concordance for 43 of 56 sites (77%). Infecton results for vertebral infections were the most notable findings in this study, despite the limited number of patients with this condition. Infecton scans were positive for hot spots in five of six patients with vertebral osteomyelitis. WBC scans showed photon-deficient areas in four of these same patients and normal distribution in the remaining two patients., Conclusion: Infecton is a useful agent for detecting infectious foci in bones and joints. Moreover, the infecton scan seems to be a more powerful tool in diagnosing vertebral infections than WBC scintigraphy.

Diabetic muscle infarction is a rare condition which may present to a rheumatologist. It was first reported in 1965. Two illustrative cases are described here and the mechanisms of pathogenesis discussed. Analysis of the published data, results of the muscle biopsies, and a technetium-99m sestamibi scan suggest that the condition, which occurs against a background of diabetic microangiopathy, can be triggered by an ischaemic event and causes extensive muscle necrosis through hypoxia-reperfusion injury and compartment syndrome.

A comparison has been made of [(123)I]meta-iodobenzylguanidine ([(123)I]MIBG) and [(111)In]pentetreotide scintigraphy in 54 patients with a variety of neuroendocrine tumors of whom 46 patients had metastatic disease. [(111)In]Pentetreotide scintigraphy was more sensitive in detecting metastatic lesions, as demonstrated on computed tomography and/or magnetic resonance scanning, than [(123)I]MIBG: 67% vs. 50% for carcinoid tumors (n = 24), 91% vs. 9% for pancreatic islet cell tumors (n = 12), 100% vs. 60% for medullary thyroid carcinomas (n = 5), and 75% vs. 100% for pheochromocytomas/paragangliomas (n = 4). In only 2 patients were lesions seen with [(123)I]MIBG scanning that were not apparent with [(111)In]pentetreotide. With the exception of pancreatic islet cell tumors, both radionuclides exhibited a similar sensitivity in detecting hepatic metastases, whereas in three patients the two radionuclides exerted a complementary role as different deposits exhibited uptake to only 1 or the other radionuclide. Hepatic metastases were the most important clinical predictor of a positive scan for both radionuclides. Neither elevated 5-hydroxyindoleacetic acid levels nor any other hormonal marker was predictive of a positive scan. In 8 patients with clinical and/or hormonal evidence of a neuroendocrine tumor but negative conventional radiology, [(111)In]pentetreotide scintigraphy was more sensitive than [(123)I]MIBG (37.5% vs. 12.5%) in detecting lesions. In conclusion, scintigraphy with [(111)In]pentetreotide detects more metastatic lesions than [(123)I]MIBG in patients with carcinoid and pancreatic islet cell tumors and medullary thyroid carcinomas; [(123)I]MIBG scintigraphy may be more sensitive for sympathoadrenomedullary tumors. The radionuclides may exert a complementary role in the detection and treatment of neuroendocrine tumors in occasional patients, as areas of different pattern of uptake were identified within the same patient. These data have implications not only for staging such tumors, but also for identifying patients who might benefit from treatment using either [(131)I]MIBG or radioactive somatostatin analogs.

Coeliac disease is diagnosed by the presence of specific antibodies and a jejunal biopsy showing mucosal atrophy and mononuclear cell infiltration. Mucosal cell-mediated immune response is considered the central event in the pathogenesis of coeliac disease, and untreated coeliac patients show specific features of T-cell activation in the small intestine. Here we describe the use of iodine-123-interleukin-2 scintigraphy in coeliac patients as a non-invasive tool for detection of lymphocytic infiltration in the small bowel and its use for therapy follow-up, and we demonstrate the specificity of binding of labelled-IL2 to activated lymphocytes by ex-vivo autoradiography of jejunal biopsies. 123I-IL2 was administered i.v. [74 MBq (2 mCi)], and gamma camera images were acquired after 1 h. Ten patients were studied with 123I-IL2 scintigraphy at diagnosis and seven were also investigated after 12-19 months of gluten-free diet. Results were expressed as target-to-background radioactivity ratios in six different bowel regions before and after the diet. At the time of diagnosis all patients showed a significantly higher bowel uptake of 123I-IL2 than normal subjects (P < 0.003 in all regions). A significant correlation was found between jejunal radioactivity and the number of IL2R + ve lymphocytes per millimetre of jejunal mucosa as detected by immunostaining of jejunal biopsy (r2 = 0.66; P = 0.008). Autoradiography of jejunal biopsies confirmed that labelled-IL2 only binds to activated T-lymphocytes infiltrating the gut mucosa. After 1 year of the diet, bowel uptake of 123I-IL2 significantly decreased in five out of six regions (P < 0.03), although two patients still had a positive IL2 scintigraphy in one region. We conclude that 123I-IL2 scintigraphy is a sensitive non-invasive technique for assessing in vivo the presence of activated mononuclear cells in the bowel of patients affected by coeliac disease. Unlike jejunal biopsy, this method provides information from the whole intestine and gives a non-invasive measure of the effectiveness of the gluten-free diet.

The size of a lymph node is not in principle a limitation for the detection of cancer by Nuclear Medicine techniques. A radioactive pinhead is detectable if it has enough radioactivity on it. The approach of Nuclear Medicine to the demonstration of impalpable lymph nodes or to those lymph nodes detected by radiological techniques that are under 1 cm as to whether or not they contain cancer, is to increase the activity attached to cancer cells in such a lymph node as much as possible and to use sophisticated image analysis techniques to distinguish such uptake from its environment. This may be undertaken using a non specific technique such as F-18 Deoxyglucose and Positron Emission Tomography which is highly sensitive and which has been successful. The alternative approach is to use a highly specific and sensitive agent, such as a radio-labelled peptide or a radio-labelled monoclonal antibody together with image analysis. This paper describes these approaches and in particular the use of Tc-99m SM3 monoclonal antibody in the detection of impalpable axillary nodes in patients with breast cancer before surgery, using a change detection analysis providing a probability map of the significance of uptake of this radiopharmaceutical. It is a robust approach, providing the patient and the surgeon with information as to the likely need for extensive axillary surgery well prior to operation. A negative study should be followed by a sentinel node evaluation at surgery.

Radiolabeled leukocyte scintigraphy is a well-established technique for the diagnosis of inflammation and infection with a typical presentation of a hot spot within the abnormal areas. However, in some cases of osteomyelitis of the axial skeleton, a cold defect pattern has been described. Tc-99m ciprofloxacin is a new agent claimed to be specific for imaging sites containing viable bacteria. In this report, we present three cases of proved bacterial infection of the axial skeleton with a mismatch pattern between Tc-99m ciprofloxin and tagged leukocytes. Although Tc-99m-labeled leukocyte scanning showed a cold defect, probably caused by bone marrow replacement, the Tc-99m ciprofloxacin consecutively revealed a hot spot at the site of infection. These data suggest that Tc-99m ciprofloxacin should be a better agent than radiolabeled leukocytes for detecting osteomyelitis of the axial skeleton.

Background: Radioimmunoscintigraphy (RIS) is being used increasingly as a new investigation in the diagnosis of recurrent colorectal cancer. This study assessed the efficacy of 99mTc-radiolabelled PR1A3 scanning in a cohort of patients with possible recurrent colorectal cancer and the effects of scan interpretation on subsequent clinical management., Methods: The scans and case notes of patients scanned over a 3-year period were reviewed., Results: Forty-seven scans in 40 patients were available for analysis. In 39 instances in which scan interpretation could be verified accurately, sensitivity for recurrent colorectal cancer was 22 of 23 (96 per cent), specificity for recurrent colorectal cancer was eight of 16 (50 per cent), positive predictive value for recurrence was 22 of 30 (73 per cent) and negative predictive value for recurrence was eight of nine (89 per cent). In 16 of the 40 patients, scan interpretation strengthened a management decision or altered management. This was beneficial to ten patients and possibly detrimental to six., Conclusion: This study demonstrated that RIS is sensitive in the detection of recurrent colorectal cancer and benefited the patient in one-quarter of cases. For the majority of patients, accurate detection of recurrent disease cannot be followed by curative therapy, but there is an important subgroup of patients in whom RIS alters management beneficially. However, a randomized prospective study is needed to confirm this.

Technetium-99m diaminocyclohexane (DACH) is a new tubular agent excreted via a cationic transport mechanism, like cyclosporine-A (CsA). It is expected that 99mTc-DACH will permit effective assessment of tubular function in CsA-treated patients. To establish the pharmacokinetic characteristics of 99mTc-DACH and to ascertain whether this new agent is useful in CsA-treated patients, 11 healthy volunteers and 15 CsA-treated patients underwent renal imaging and clearance studies using 99mTc-DACH and chromium-51 ethylene diamine tetra-acetic acid (EDTA). 99mTc-DACH yielded satisfactory dynamic renal images in all participants. The mean plasma clearance of 99mTc-DACH was significantly greater than that of 51Cr-EDTA in volunteers (109.4¿19.7 ml/min versus 86.6 +/- 13.7 ml/min, P<0.05). However, the urinary excretion of 99mTc-DACH at 90 min was significantly lower than that of 51Cr-EDTA (46.1% +/- 9.3% versus 53.1% +/- 8.6%, P<0.05), most probably due to its partial parenchymal retention. The elimination half-life of 99mTc-DACH was significantly increased in CsA-treated patients in comparison to volunteers, and consequently the plasma clearance values were significantly suppressed in these patients, in contrast to 51Cr-EDTA and endogenous creatinine clearance values. In conclusion, our findings indicate that 99mTc-DACH, as a sensitive marker of cationic tubular function, could be used to monitor renal haemodynamics in patients receiving CsA treatment.

Secondary tumours of any type in the breast are rare. A review of the literature demonstrated only 23 cases of carcinoid tumours with associated breast metastasis, as distinct from primary carcinoid tumours of the breast. Distant metastases from carcinoid tumours are correlated with poor prognosis and survival. Although both primary and metastatic mammary carcinoid tumours are uncommon, the recognition of the true origin of the tumours may be of importance owing to the different clinical management and prognosis of the two conditions. Recently, radionuclide-labelled imaging techniques have been applied to the localization of such lesions, based on isotope uptake by receptors present in these neuroendocrine tumours. We report two new cases of carcinoid tumours with breast metastases, the primaries being in the ileocaecal valve and the bronchus, respectively. The diagnosis of a carcinoid tumour was based on the clinical, biochemical, histopathological and immunostaining features. Furthermore, these patients had both 123I-MIBG and 111In pentetreotide scintigraphy performed. These radionuclides play a useful role in the localization and potentially in the management of carcinoid tumours and their distant metastases.

Pendred syndrome comprises the association of severe congenital sensorineural deafness with thyroid pathology. Although it is the commonest form of syndromic hearing loss, the primary genetic defect remains unknown. The variable clinical presentation allied to the difficulty in securing the diagnosis have resulted in relatively poor documentation of the radiological features of this syndrome. We now present data on 40 patients, all complying with strict diagnostic criteria for the disorder, and describe our experience of the prevalence of specific malformations of the inner ear as well as comparing the relative merits of computed tomography (CT) and magnetic resonance imaging (MRI) in the investigation of this inherited condition. Deficiency of the interscalar septum in the distal coils of the cochlea (Mondini deformity) was found to be a common but probably not a constant feature of Pendred syndrome. However, enlargement of the endolymphatic sac and duct in association with a large vestibular aqueduct was present in all 20 patients examined by MRI. We conclude that thin section high resolution MRI on a T2 protocol in the axial and sagittal planes is the imaging investigation of choice.

Aims: To determine the sensitivity and specificity of 99mTc-Infecton (Infecton), a novel ciprofloxacin based imaging agent, in detecting sites of infection., Methods: Ninety patients thought to be suffering from a variety of infections were administered 300-400 MBq of Infecton intravenously. Whole body images were taken one and four hours later. Appropriate specimens were taken for microbiological investigations. Statistical analysis was performed using a computer statistical package., Results: Ninety eight Infecton images were produced. Forty one of these were positive, including three false positives, where the patients had non-infective conditions. Fifty seven negative images were obtained, of which 41 were true negatives and 16 were false negatives, having definite evidence of infection. Thus, Infecton imaging has a sensitivity of 70.3% and a specificity of 93.1% for detecting infective foci. The positive and negative predictive values were 92.6% and 71.9%, respectively., Conclusion: Infecton imaging is a new diagnostic tool that is specific for detecting sites of bacterial infection in the body. The high positive predictive value displayed by the technique is clinically important because a positive image strongly supports a diagnosis of bacterial infection. A negative result does not rule out an infection, and may be a result of previous or current antibiotic treatment and/or infection with organisms that do not take up Infecton. Infecton imaging has major advantages over well established imaging techniques, including radiolabelled leucocytes, and may prove to be a superior method for localising bacterial infections.

A medical image without the relevant associated data is of no value. What is relevant depends on the use which is to be made of the image. The associated data may be divided into groups associated with the patient, the image data (array size, data type), the image itself (e.g. acquisition method), the requested imaging procedure to which it belongs, graphical, numerical and time information associated with the images, relevant results of other medical procedures, etc. Images, digital images and the associated data must be managed in an efficient manner in order to deliver appropriate patient care. In order to realise fully the potential of digital imaging, digital image data must be transmitted from acquisition units and stored in such a way as to allow appropriate access to health care practitioners in the imaging department, hospital and community. Standards exist for the formatting and transmission of image and related data (Digital Imaging and Communications in Medicine (DICOM). NEMA PS 3.1-PS3.12, The National Electrical Manufacturers Association, Rosslyn, VA, 1992, 1993, 1995; Health Level Seven, An Application Protocol for Electronic Data Exchange In Healthcare Environment, version 2.2, Health Level Seven Inc., Ann Arbor, MI, 1994; Comite European de Normalisation, Technical Committee 251: Medical Informatics) although further work is required in order to improve interoperability. There is some overlap in current standards, thus an important area is the agreement on the scope of the work to be done by different bodies. Standards are lacking in the areas of image management and presentation. Strategies for the efficient use of a memory hierarchy to achieve satisfactory archiving and access must be developed and this depends on the existence of appropriate descriptive data fields. Specific issues exist regarding security of image data. Key areas requiring immediate work are the profiling of descriptive data elements according to different clinical application needs in order to improve interoperability and the development of strategies for evolution from legacy systems to modern networked systems. The best way forward is to consolidate and refine existing specifications.

This review article forecasts developments in nuclear medicine instrumentation which are on the horizon. Special attention is paid to the physical properties of detectors and multiple-processor parallel processing systems needed for fast and high-quality imaging in emission tomography. Advances in detector technology will improve imaging resolution below 5 mm and will increase sensitivity and quantitative accuracy. In addition, high count rate list-mode acquisition enables 'true' four-dimensional data-sets. A sandwich-like construction of two different crystals allows the simultaneous use of conventional tracers and positron tracers (multiple emission tomography, MET). Transmission-based attenuation and scatter compensation with fast iterative reconstruction methods will further improve image quality. The clinical and scientific importance of improved images and the limits on advances in instrumentation are also reviewed.

The aim of the study was a quantitative comparison of relative renal uptake and both the whole-kidney and the parenchymal transit time derived from factor analysis of image sequences and provided by standard clinical procedues. In order to extract the stable, well-interpretable factors, factor analysis was performed locally in the problem-specific time and spatial windows and the resulting factor images either evaluated directly as functional images or used as fuzzy regions of interest (ROIs) for the subsequent extraction of time-activity curves from the analysed data. The values of relative renal uptake of the left kidney measured in the functional factor images, which demonstrate the initial accumulation of activity in renal parenchyma (mean 51.0%), did not differ significantly from the values obtained by a standard method (mean 51.5%, r = 0.98, P<0.001). Whole-kidney transit time calculated using fuzzy ROI curves correlated well with the reference values (r = 0.84, P<0.001); however, both its mean value (336.5 s) and the standard deviation (151.5 s) were substantially greater than those of the values provided by a standard procedure (262.8+/-86.9 s). Parenchymal transit time calculated using ROI curves correlated better with the transit time through a wider corticomedullary region rather than through a narrow cortical region, which is decisive in a differential diagnosis of renal disorders. In general, values of transit times provided by factor analysis correlated well with those provided by reference methods but with a shift towards the higher numerical values. This may have been a consequence of a greater extent of the automatically extracted fuzzy ROIs, or of occasionally delayed accumulation in the upper calyces. Results of the study provide quantitative evidence that the factor analysis of dynamic data, even without the introduction of prior physiological information, may yield clinically relevant information. However, some basic requirements, such as sufficiently high sampling frequency and count rate, adaption of the method to a specific clinical task, and proper selection of time and spatial windows for locally performed analysis, have to be fullfilled if the method is to be successfully applied clinically.

Imaging and therapy of cancer using radionuclide-labelled compounds is surveyed. The current state of knowledge concerning the cancerous process, the subtle differences between the cancer cell and the normal cell, and the biological basis of the response of cells to low-level and internal targeted radiation are described. There is movement from the surface of the cancer cell with antigen, receptor and transport protein detection, to the cytoplasm with the monitoring of signal transduction and gene therapy, to the nucleus with oligonucleotides antisense to oncogenes. Nuclear medicine's shift from physics to biology is from the nucleus of the atom to the nucleus of the cell.

Pendred syndrome is an autosomal recessive condition classically characterized by deafness and goitre. Since both cochlear and thyroid pathology are required to secure the diagnosis, it is unclear whether the condition might present without the classical features. The perchlorate discharge test, the gold-standard investigation for Pendred syndrome, is non-specific, and in the absence of alternative means of confirming the diagnosis, its sensitivity is unknown. We used the recent mapping of the gene to chromosome 7q to identify pedigrees with a likely diagnosis of Pendred syndrome, and assessed the prevalence of clinical parameters of disease in affected patients. Thirty-six familial cases showed co-segregation between disease and the Pendred syndrome locus on chromosome 7q. Clinical and investigative findings were compared in index cases (n = 18) vs. affected siblings (n = 18). The overall prevalence of goitre was 73%, higher in index cases (94%) than in siblings (56%), many of whom had not previously been considered to have the condition. One perchlorate discharge test was false-negative (2.9%). Radiological malformations of the cochlea were identified in 86% of cases. Securing a diagnosis of Pendred syndrome may be difficult, especially in the single case. The perchlorate discharge test, although valuable, is difficult to undertake in the younger patient, and radiology may assist in diagnosing such patients.

Aim: To determine the contributions of gastrointestinal transit and pouch characteristics to bowel frequency in patients with an ileoanal reservoir and no pouchitis., Methods: Twenty one patients who had undergone restorative proctocolectomy, with ileostomy closure at least eight months previously, and who had no history of pouchitis were recruited. They were prospectively classified on the basis of their bowel frequency: 11 patients had good pouch function (bowel frequency less than six per day) and 10 had poor function (bowel frequency more than six per day). Gastrointestinal transit was studied using a dual isotope technique and anal and pouch physiological examination was performed on all patients., Results: Lag phase, 25% and 50% gastric emptying, small bowel transit time, and 10% and 50% pouch filling times, all for solids and liquids, were not significantly different between patients with good and poor function. Anal manometry and pouch and anal electrical sensitivity were also similar in the two groups. The volume of air and water required to elicit an initial sensation and the urge to defaecate were similar in both groups, but the maximum tolerated volume to both air (525 v 245 ml, good v poor function, median values) and water (625 v 370 ml) infusion was significantly (both p < 0.02) lower in patients with poor function., Conclusion: Maximum tolerated volume in the pouch, which may reflect pouch size, sensitivity, compliance, or a combination of these is the major determinant of pouch function. Gastrointestinal transit does not seem to be an important determinant of function.

Attachment of chelating agents to the sugar residues of antibodies for subsequent radiolabelling is an attractive approach since it may have less effect on the immunoreactivity than attachment through lysine residues, which are distributed throughout the antibody and may be present near the antigen binding site. We have attached a new hydrazide-linked chelator CYT-395 (Cytogen Corp., Princeton, N.J.) to the sugar residues of the anti-prostate monoclonal antibody 7E11C5.3 and optimised the conditions for labelling the conjugate with technetium-99m in order to compare the conjugate to 7E11C5.3 antibody labelled directly with technetium using a mercaptoethanol reduction technique. Labelling yields of 70%-90% were obtained at specific activities up to 2000 MBq/mg antibody. The stability of the technetium-labelled conjugate in plasma or to a challenge with 0.1 or 1.0 mM cysteine was similar to that of direct-labelled antibody. In nine patients with prostate cancer, the plasma clearance of the labelled conjugate followed a two-compartment model, with an average beta-phase half-life of 31.4+/-3.9 h. The average urinary clearance at 24 h was 15.3+/-5.0% of the injected dose. In this group of patients there was no significant difference between the blood and urine clearance of the labelled conjugate, and the clearances of the direct-labelled antibody.

Unlabelled: To evaluate the performance of the 99mTc-labeled monoclonal antibody CYT-351 in visualizing prostate cancer, radioimmunoscintigraphy (RIS) was performed in 35 patients., Methods: Antibody (0.5 mg) labeled with 600 MBq 99mTc was injected intravenously after obtaining informed consent. Planar and SPECT imaging was performed at 10 min and 6-8 and 22-24 hr postinjection. The scans were evaluated for visualization of the primary focus or local recurrence, extraprostatic invasion, lymph node involvement and uptake in bone and soft tissue metastases., Results: Thirty-six studies in 35 patients were performed. In 13/14 evaluable studies with clinically localized prostate cancer, RIS had a true-positive rate of 92% (12/13). In eight patients with previous incidental carcinoma detected during transurethral resection undertaken for clinically benign disease, there were 86% true-positive results (6/7) and one true-negative result, which were confirmed by systematic needle biopsies. In six patients with evidence of local recurrence after a previous radical prostatectomy, the true-positive rate was 100% (6/6), which was confirmed by raised or rising prostate-specific antigen levels (PSA) and/or by biopsy. In the eight patients with known metastases, the disease was visualized in 4/4 with progression but not in the 3/3 with regression; one patient demonstrated regressing disease as determined by PSA levels. The overall accuracy was 92%., Conclusion: RIS with 99mTc CYT-351 is capable of providing good quality images and yielding clinically useful information safely. It has a potentially important clinical role for patients with rising PSA levels but negative images by conventional modalities.

The aim of the study was to distinguish infection from inflammation in patients with suspected infection using technetium-99m Infecton. Ninety-nine patients (102 studies) referred for infection evaluation underwent imaging with 400 MBq 99mTc-Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and about half (56) had radiolabelled white cell scans as well. No adverse effects were noted in any patient. The clinical efficacy of 99mTc-Infecton depended in part on whether imaging was undertaken during antibiotic therapy for infection or not. In consultation with the microbiologist, 5-14 days of appropriate and successful antibiotic therapy was considered adequate to classify some results as true-negatives. The figures for sensitivity and specificity of 99mTc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that 99mTc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected.

Background: Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as thallium-technetium subtraction imaging in the preoperative localization of hyperplastic parathyroid glands in patients with renal failure. Reports have suggested that 50% of glands can be identified correctly by this method. The aim of this study was to improve on previous results and demonstrate that Tc-99m MIBI imaging has an important place in the preoperative work-up of these patients., Methods: Eighteen patients on renal replacement therapy were studied. All had tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method was employed. The imaging results were compared to the subsequent surgical and histological findings., Results: In the 12 patients in whom serum parathyroid hormone levels fell postoperatively to within or below the normal range, 38 of 46 glands (82.6%) were correctly identified and located in the correct quadrant of the thyroid gland. There were two false positive results where the imaging predicted glands not subsequently found by the surgeon. In the patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate accurately the site of the residual parathyroid tissue., Conclusions: Tc-99m MIBI imaging is able to identify more than 80% of hyperplastic parathyroid glands in renal failure patients if this reporting process is used, and locate them in the correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value when re-exploration of the neck is required for post-parathyroidectomy hyperparathyroidism. These results represent a significant improvement on the sensitivity of this imaging technique when compared to previous published data.

Renal radionuclide studies have progressed from the probe to the gamma camera and sophisticated hard- and software, yet the principles remain the same. Many of the problems were identified and the solutions proposed 25 years ago, but these solutions are still not applied in practice. This survey charts the evolution of renography during this period.

Purpose: In patients with idiopathic megarectum, it is unknown whether abnormality is limited to the dilated large bowel or whether the upper gut is abnormal, as in the various forms of chronic intestinal pseudo-obstruction. This has important implications for treatment, especially surgery., Methods: Ten patients (4 females; median age, 18 (range, 17-26) years) with idiopathic megarectum had contrast studies of the upper and lower gut, radioisotope (technetium-99m liquid and indium-111 solid phase) measurement of gastric, small-bowel, and colonic regional transit, and radiopaque marker colonic studies., Results: All patients had a dilated large bowel. No patient had radiographic evidence of upper gut dilation. Four patients had normal and six patients had abnormally slow gastric emptying. Both the radioisotope scans and radiopaque marker studies showed abnormal colonic transit. Regions of delay corresponded with the region of dilated bowel. Symptoms of abdominal distention and bloating did not correspond to abnormalities of gastric emptying but rather with effectiveness of rectal evacuation., Conclusion: Patients with idiopathic megarectum have abnormal colonic transit, delay occurring predominantly in the dilated gut. Marker studies are less sensitive than isotope studies but provide adequate information for clinical purposes. Although motility abnormalities of the upper gut are common, symptoms correlate with large-bowel abnormalities.

Objective: Pendred's syndrome is an association between congenital neurosensory deafness and goitre with abnormal discharge of iodide following perchlorate challenge, indicating a defect of iodide organification. Although Pendred's syndrome may cause up to 7.5% of all cases of congenital deafness, the molecular basis of the association between the hearing loss and the thyroid organification defect remains unknown. We chose to investigate the role of the thyroid peroxidase (TPO) gene as the genetic defect in Pendred's syndrome., Design: A highly informative variable number tandem repeat (VNTR), located 1.5 kb downstream of exon 10 of the TPO gene, was used to search for genetic linkage in multiple sibships affected by Pendred's syndrome., Patients: Seven kindreds were recruited from the UK, each with at least two affected members. We have also examined a large inbred Israeli family with two affected offspring and five unaffected children., Measurements: Individuals were assigned affected status based on the characteristic clinical features of Pendred's syndrome, namely the presence of congenital sensorineural hearing loss and the appearance in early life of a goitre. Additionally, at least one affected member from each sibship had a characteristic positive perchlorate discharge test (Morgans & Trotter, 1958). PCR amplification of genomic DNA at the TPO VNTR allowed assignment of genotypes to each individual and the calculation of a two-point LOD score., Results: In six of the nine sibships analysed we found obligatory recombination between TPO and Pendred's syndrome. Non-complementation observed in affected parents with an affected offspring excluded TPO in an affected sibship with genotype sharing and supports a hypothesis of genetic homogeneity for Pendred's syndrome. In two sibships, mutation of the TPO gene as the cause of Pendred's syndrome could not be excluded., Conclusions: These data suggest that defects at the thyroid peroxidase locus on chromosome 2 are not the major cause of Pendred's syndrome.

A wide range of antibody fragments can be expressed in bacteria and detected immunochemically via peptide tags. Using specially designed tags, we have developed a strategy for radiolabeling antibody fragments secreted from bacteria. Tagged antibody fragments were secreted either into the bacterial periplasm or the culture medium. The tag was not subject to proteolysis either in the broth or in human plasma. After affinity purification the antibody fragments were phosphorylated with [gamma-32P]ATP and casein kinase II. The labeled fragments were used in a gel band-shift assay to measure antigen binding affinities. In contrast to non site-specific methods such as radioiodination, antibodies labeled with casein kinase II retain full immunoreactivity. Radioactively phosphorylated antibody fragments may have many other applications, including radioimmunoassays and radioimmunotherapy.

Objective: To investigate the clinical application of a new technique for imaging prostatic malignancy using planar imaging and single-photon emission tomography (SPET) with technetium-99m-labelled antibody to a prostatic cell surface membrane antigen., Patients and Methods: Prostatic malignancy was imaged by radioimmunoscintigraphy (RIS) using a 99mTc-labelled monoclonal antibody, CYT-351, raised against a newly identified membrane antigen present in normal and malignant prostatic tissues. The protocol involved taking serial images and assessing the changes in activity, as the uptake of specific antibody increased with time and non-specific uptake decreased. Data from planar images were collected at 10 min, 6 and 24 h after injection with antibody, and by SPET at 6 and 24 h using a Siemens Orbiter Large Field of View gamma camera. Twenty-two RIS scans were evaluated, which included six patients with clinically localized disease, six patients with previous incidental carcinoma at prostatectomy for apparently benign disease, four patients with evidence of local recurrence after radical prostatectomy and six patients with metastatic disease., Results: Primary tumours and secondary lymphatic and bone metastases were demonstrated. Only one minor side-effect was experienced., Conclusion: This RIS technique was capable of imaging primary prostatic malignancy and metastatic disease in lymph nodes and bone. Its clinical application remains to be defined, but potentially it provides a new means for tumour staging based upon tissue characterization. It may be particularly useful before radical prostatectomy and it is capable of imaging local recurrence following radical treatment of localized disease. Future applications include monitoring the progression of disease and the response to treatment.

Background: Bacterial infection can pose a substantial diagnostic dilemma. Techniques involving radiolabelled leucocytes can pinpoint the site of inflammation. However, previous radiolabelling techniques have failed to distinguish between bacterial-mediated infection and non-bacterial inflammation. To overcome this difficulty, we have studied a radiopharmaceutical, technetium-99m (99mTc) Infecton, which is based on the antibiotic ciprofloxacin., Methods: We used this agent to image bacterial infection in 56 patients (one twice) with known or suspected sites of infection. We then compared the imaging results of these patients with those from a radiolabelled leucocyte study., Findings: The concordance rate was 68% (39 out of 57 images). In 18 discordant results 99mTc Infecton was correctly positive in 8 out of 9 positive studies and correctly negative in 4 out of 9 negative studies. 4 out of 5 of the falsely negative studies were in patients who had taken antibiotics for over 7 days. We found that 99mTc Infecton gave better imaging results than radiolabelled leucocytes. Comparison between 99mTc Infecton and leucocyte imaging gave sensitivities of 84% and 81%, and specificities of 96% and 77%, respectively., Interpretation: We believe that the specificity 99mTc Infecton confers for bacterial infection and its ease of administration are the main advantages of this new agent.

Primary hyperparathyroidism is a common condition due to either a parathyroid adenoma or, less commonly, parathyroid hyperplasia, whose treatment is essentially surgical. We have, therefore, assessed the accuracy of Tc-99m pertechnetate/Tc-99m sestamibi (methoxy-isobutyl isonitrile) imaging in the localization of adenomas and hyperplastic parathyroids. The clinical records of all patients who had Tc-99m pertechnetate/Tc-99m sestamibi imaging and parathyroid surgery at this hospital were reviewed. The technique used involves standard subtraction methodology with the addition of a novel change detection algorithm to optimize localization. Of 46 patients scanned in 48 patient episodes, 36 patients had adenomas; 28 (78%) were accurately localized to the correct quadrant, and 4 were correctly lateralized. Two patients with parathyroid carcinomas had their metastases correctly localized. Thus, in 34 of 38 (89.5%) of the scans, adenomas or carcinomas were able to be anatomically localized. Six patients presented with hyperplasia; 5 were diagnosed by sestamibi scans, and 3 of these accurately localized all hyperplastic glands. Four additional patients had known hyperplasia, of which 2 were rendered normocalcemic after removal of their sestamibi-positive glands; the other 2 had small second glands detected only at surgery. In patients with unknown pathology, imaging suggested that 6 patients had hyperplasia; this was correct in 5 cases (83%). Nine of the 12 scans in patients who had had previous parathyroid surgery accurately localized the tumors, 7 in the neck and 2 outside. We suggest that sestamibi imaging can help to distinguish hyperplasia from adenomatous disease; when imaging is required, we recommend it as the imaging modality of choice in all patients with primary hyperparathyroidism, especially in reoperated patients.

99mTc SM3 radioimmunoscintigraphy is combined with kinetic analysis and probability mapping using a change detection algorithm to investigate axillary node involvement before primary surgery in patients with breast cancer. Whereas planar imaging was unsuccessful, axillary node involvement was correctly determined in 11 out of 13 patients 6 out of 7 true negatives and 5 out of 6 true positives down to 0.35 grams. A prospective study is underway.

One of the subtle differences between the cancer cell surface and the normal cell is exploited by immunoscintigraphy. The clinical role and some technical aspects of imaging cancer with radiolabelled antibodies are reviewed. 99mTc is the best radiolabel for immunoscintigraphy. Specificity is added to the general sensitivity of nuclear medicine techniques by this approach to imaging cancer.

The papers of the 4th Scandinavian Symposium on Radiolabeled Monoclonal Antibodies in Diagnosis and Therapy of Cancer are summarised. Particular emphasis is placed on quantitation, dosimetry and radionuclide therapy. Some biological aspects of radionuclide therapy are indicated.

Watershed infarction has previously been described after cerebral trauma, when it is due to raised intracranial pressure or systemic hypotension. A case is reported, so far as is known for the first time, of bilateral watershed infarction following blunt systemic trauma, without injury to the head or neck. The importance of resuscitation in preventing secondary brain injury caused by systemic hypotension is highlighted. The advantages of HMPAO-SPET in detecting cerebral perfusion defects are discussed.

The impact of recent advances in the chemical and genetic engineering manipulations of antibodies on radioimmunotargeting is reviewed both in relation to radioimmunoscintigraphy and radioimmunotherapy. The resulting trends are: (1) the linking of parts of the mouse/rat and human antibody molecule; (2) the creation of molecules with dual antigen or multiple antigen recognition capabilities; (3) the making of smaller and smaller antigen recognition molecules; and (4) the development of molecules with dual capabilities, e.g. antigen recognition and enzyme activity. The various methods of creating antibodies in vitro are reviewed with reference to bacteria, using phage selection and a combinatorial library, mammalian cells, yeast cells and, finally, mice containing giant yeast artificial chromosomes. The advantages and disadvantages of smaller fragments as well as of the human anti-mouse antibody (HAMA) reaction are discussed and the need for early clinical evaluation and widespread availability of the newer antibodies is emphasized. It is envisaged that these immunotechnological advances will permit the large-scale production of precisely engineered humanized antibodies, and the specificity and affinity rate constant of these antibodies can be optimized using in vitro phage selection as well as by computer modelling where the stereo chemistry of the antigen is known precisely.

Parathyroid tissue is sometimes auto-transplanted into the forearm after 'total' parathyroidectomy in patients with renal failure. Recurrent hyperparathyroidism demands identification of the source of PTH secretion which cannot be assumed to be the forearm. To this end, Tc-99m methoxy isobutyl isonitrile (MIBI) scintigraphy was used to identify functioning auto-transplanted parathyroid tissue in seven patients undergoing renal replacement therapy (five with functioning renal transplants and two on haemodialysis). Serum PTH was estimated in venous blood taken proximal and distal to the forearm graft and from the contralateral arm, and subsequent Tc-99m MIBI scanning was carried out without knowledge of the PTH results. Five patients had a significant gradient in PTH levels between sites proximal and distal to the graft, and between the proximal site and the contralateral arm, suggesting functioning parathyroid tissue in the graft. Subsequent Tc-99m MIBI scintigraphy confirmed the activity of the auto-transplanted parathyroid tissue in these five patients. In the remaining two patients without a significant PTH gradient between the sampling sites, Tc-99m MIBI scintigraphy did not identify any functioning forearm parathyroid tissue. The scan results therefore correlated well with the gradients in PTH levels, suggesting that MIBI scintigraphy can be used to identify functioning auto-transplanted parathyroid tissue. The results also indicate that any patient who has undergone auto-transplantation of parathyroid tissue must have blood samples taken from veins proximal to the graft and either distal to it, or from the contralateral arm when parathyroid status is re-assessed, particularly when surgery is being considered for recurrent hyperparathyroidism.

Captopril renography was utilized to assess the presence of angiotensin II dependent renovascular dysfunction in (1) 28 patients with mild to moderate essential hypertension (EH) with unimpaired renal function, and (2) 25 hypertensive patients with diabetic nephropathy (HDN). These studies were classified according to the diagnostic criteria outlined by the Working Party on Diagnostic Criteria of Renovascular Hypertension with Captopril Renography and the mean parenchymal transit time (MPTT) was used as an index for detecting the presence of angiotensin II dependent renal haemodynamic change. Patients with EH showed non-significant or non-specific alterations in the MPTT. Four patients in the HDN group showed a significant prolongation of MPTT in the presence of renin-angiotensin-aldosterone activation due to renal artery stenosis, and the other patients in this group showed a significant decrease in MPTT after captopril, consistent with increased blood flow and improved tubular transport function in the presence of microangiopathy only. We conclude that addition of MPTT to the standard diagnostic criteria of captopril renography may be helpful in predicting the beneficial or detrimental impact of angiotensin II inhibition treatment in HDN and in limiting the test protocol in EH to one post-captopril study.