K. E. Britton

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

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

Radiological malformations of the ear in pendred syndrome

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.

Comparison of 99mTc infecton imaging with radiolabelled white-cell imaging in the evaluation of bacterial infection.

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.

Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection.

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 MBq99mTc-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 of99mTc-Infecton depended in part on whether imaging was undertaken during intibiotic 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 of99mTc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that99mTc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected.

Imaging bacterial infection with 99mTc-ciprofloxacin (Infecton)

Aims: The diagnosis of deep seated bacterial infections, such as intra-abdominal abscesses, endocarditis, and osteomyelitis, can be difficult and delayed, thereby compromising effective treatment. This study assessed the efficacy of a new radioimaging agent, Tc-99m ciprofloxacin (Infecton), in accurately detecting sites of bacterial infection. Methods: Eight hundred and seventy nine patients with suspected bacterial infection underwent Infecton imaging and microbiological evaluation. The sensitivity and specificity of Infecton in detecting sites of bacterial infection were determined with respect to Centres of Disease Control, World Health Organisation, and Dukes’s criteria. Results: Five hundred and seventy four positive and 295 negative images were produced. These included 528 true positives, 46 false positives, 205 true negatives and 90 false negatives, giving an overall sensitivity of 85.4% and a specificity of 81.7% for detecting infective foci. Sensitivity was higher (87.6%) in microbiologically confirmed infections. Conclusions: Infecton is a sensitive technique, which aids in the earlier detection and treatment of a wide variety of deep seated bacterial infections. The ability to localise infective foci accurately is also important for surgical intervention, such as drainage of abscesses. In addition, serial imaging with Infecton might be useful in monitoring clinical response and optimising the duration of antimicrobial treatment.

Evaluation of the efficacy of 99mTc-Infecton, a novel agent for detecting sites of infection.

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.

Treatment of metastatic carcinoid tumours, phaeochromocytoma, paraganglioma and medullary carcinoma of the thyroid with 131I-meta-iodobenzylguanidine (131I-mIBG)

OBJECTIVE Meta‐iodo‐benzyl‐guanidine labelled with 131‐iodine (131I‐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 131I‐mIBG, we have reviewed all patients who had received this form of treatment in our department.

Gastrointestinal transit and prolonged ambulatory colonic motility in health and faecal incontinence

Background—Colonic motor function has not been studied in the ambulatory setting over a prolonged period in the unprepared state. Furthermore, the disturbance of this function in patients with faecal incontinence is unknown. Aim—To study colonic function over two to three days in the ambulatory, unprepared state in health and in patients with idiopathic faecal incontinence. Methods—Six healthy women and six women with faecal incontinence and a structurally intact anal sphincter ingested a dual radioisotope meal, and had a six sensor, solid state manometric probe colonoscopically inserted into the left colon. Scanning was performed until radioisotope left the gut and pressure was recorded for a median of 44 hours. Results—Three of six patients showed abnormal gastric emptying. Patients showed no disturbance of colonic radioisotope transit. Controls had a median of 12, whereas patients had a median of 16, high amplitude propagated waves per 24 hours. In three patients urge incontinence was associated with high amplitude (up to 500 cm water) propagated waves which often reached the rectum. These high pressure waves were identical to those occuring in healthy subjects, the only difference being the lack of adequate sphincter response. Passive incontinence was not associated with colonic motor activity. Defaecation in all subjects was associated with identical propagated waves, and distal movement of 13% (median) of right colonic content and excretion of 32% from the left colon and rectum. The urge to defaecate was associated with either propagated waves (45%) or non-propagated contractions (55%). Rectal motor complexes were recorded in both groups of subjects, but similar rhythmic activity was also recorded in the sigmoid and descending colon. Conclusions—Normal colonic function consists of frequent high pressure propagated waves. Rhythmic activity occurs both proximal to and in the rectum. Defaecation is characterised by high pressure propagated waves associated with coordinated anal sphincter relaxation. Patients with faecal incontinence may have a widespread disturbance of gut function. Urge incontinence, an urge to defaecate, and defaecation can all be associated with identical high amplitude propagated pressure waves.

Prevalence, age of onset, and natural history of thyroid disease in Pendred syndrome

BACKGROUND We have sought to establish the prevalence of goitre within a Pendred syndrome (PS) cohort and to document the course of thyroid disease in this patient group. As part of a genetic study of PS we have assessed 57 subjects by perchlorate discharge test and in 52 (M 21, F 31, age range 9-54 years) a discharge of radioiodide of >10% was observed. RESULTS Goitre was present in 43 (83%) of the cohort (28 F, 15 M), generally developing after the age of 10 years, 56% remained euthyroid (age range 9-37 years), and 19 patients (44%) had objective evidence of hypothyroidism, all of whom had goitre. CONCLUSIONS In summary, thyroid dysfunction in PS is variable and inclusion of goitre as a diagnostic requirement will maintain significant underascertainment. The recent identification of the genetic defect underlying PS is likely to provide an important diagnostic aid in the identification of this disorder and this communication should assist clinicians in identifying deaf patients who ought to be considered for this investigation.

Summary and Perspectives

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