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A risk of malignancy index (RMI), based on menopausal status, ultrasound (US) findings, and serum CA125, has previously been described and validated in the primary evaluation of women with adnexal masses and is widely used in selective referral of women from local cancer units to specialized cancer centers. Additional imaging modalities could be useful for further characterization of adnexal masses in this group of women. A prospective cohort study was conducted of 196 women with an adnexal mass referred to a teaching hospital for diagnosis and management. Follow-up data was obtained for 180 women; 119 women had benign and 61 women malignant adnexal masses. The sensitivity and specificity of specialist US, magnetic resonance imaging (MRI), radioimmunoscintigraphy (RS), and the RMI were determined. We identified a subgroup of women with RMI values of 25–1000 where the value of further specialist imaging was evaluated. Sensitivity and specificity for specialist US were 100% and 57%, for MRI 92% and 86%, and for RS 76% and 87%, respectively. Analysis of 123 patients managed sequentially, using RMI cutoff values of ≥25 and

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.

The purpose of this study was to compare the utility of 99mTc labelled ciprofloxacin (Infecton) imaging with the 99mTc white blood cell and three-phase bone imaging procedures for identifying hip prosthesis infection. We studied 30 symptomatic patients in whom infection was confirmed in eight and excluded in 22 cases based on clinical and microbiological findings. 99mTc ciprofloxacin images were obtained at 1, 4 and 24 h after the injection of the tracer, and the data were compared to those obtained from 99mTc leukocyte and three-phase bone imaging. The 99mTc ciprofloxacin imaging correctly identified all true infections. In 13 (59%) of the non-infected patients, non-specific uptake of 99mTc ciprofloxacin was found in the 1-h and 4-h images, which disappeared, however, in the 24-h images. When the early and late 99mTc ciprofloxacin images were compared, the specificity was found to improve from 41% to 95%, positive predictive value from 38% to 89%, and the diagnostic accuracy from 57% to 97%. The accuracy of the conventional 99mTc leukocyte imaging was 90%. Dynamic bone imaging also yielded abnormal findings in all the infected patients although also in 23% of the non-infected patients. Current data indicate that 99mTc ciprofloxacin is a useful method for confirming hip prosthesis infection. The diagnostic efficiency of this method is improved when the imaging time is extended to 24 h post-injection of the tracer.

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.

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.

1Department of Physics and Nuclear Medicine, City Hospital, Birmingham, 2Department of Medical Physics and Clinical Engineering, Royal Hallamshire Hospital, Sheffield, 3Department of Nuclear Medicine, Southampton General Hospital, Southampton, 4Department of Nuclear Medicine, St Thomas’ Hospital, London, 5Department of Medical Physics, Manchester Royal Infirmary, Manchester and 6Department of Nuclear Cardiology, Leeds General Infirmary, Leeds, UK

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.

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.

The labelling of interleukin-2 (IL-2) with 123I and its in vivo application for imaging chronic pathological lymphocytic infiltrations are described. The lactoperoxidase/glucoseoxidase technique was the labelling method of choice leading to immunoreactive IL-2 with high specific activity. Labelled IL-2 was injected in diabetes-prone non-obese diabetic (NOD) mice with pancreatic lymphocytic infiltration. As control animals, Balb/c mice were used. As specificity control, monoclonal antibodies AMT13 and UCHT1, bovine serum albumin and alpha-lactalbumin were radioiodinated and injected in mice. Eighteen NOD mice and four control Balb/c mice were used for gamma camera imaging experiments. Fifty-four NOD and 20 Balb/c mice were used for time course single organ counting and autoradiography. Gamma camera images showed that radioactivity accumulated in the pancreatic region from the 10th minute onwards in NOD mice injected with 123I-IL-2 but not in Balb/c mice, or in NOD mice injected with control radiopharmaceuticals. These findings were confirmed by counting the radioactivity present in single organs. Autoradiography of NOD pancreas, after injection of labelled IL-2, showed that radioactivity was specifically associated with infiltrating lymphocytes. In conclusion, this technique is highly specific and easy to perform and we suggest its application in humans for in vivo detection of areas of lymphocytic infiltration.

The aim of this study is to determine whether white blood cell imaging in inflammatory conditions is due to a blood pool effect as a result of an increased vascularity and vascular permeability, or whether cellular migration is the major contributing factor. It will be shown that white cell uptake is a specific phenomenon in the rheumatoid knee joint and not just a blood pool effect.

The clinical applications of this approach to the management of patients with ovarian cancer and of patients with colorectal cancer are emphasized. The introduction of stable 99Tcm labelling of monoclonal antibodies means that radioimmunoscintigraphy is able to become routinely available in nuclear medicine departments.

A new monoclonal antibody, SM3, against stripped mucin core protein has been evaluated for the radioimmunoscintigraphy of ovarian cancer. It was radiolabelled with In-111, I-123 and Tc-99m and results showed a sensitivity of 95%, 100% and 100% and an accuracy of 73%, 86% and 100% for malignancy; respectively.

Summary 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.

Pendred syndrome is an autosomal recessive inherited disorder characterized by profound hearing impairment and inappropriate iodine release by the thyroid on perchlorate challenge. Thirty-three cases comprising members of 13 families and eight isolated cases were studied, with detailed audiological and vestibular investigation and computerized tomography. A uniform, profound, symmetrical sensorineural hearing loss was identified in all cases. Approximately one-third of the group reported progressive hearing impairment, in childhood or adolescence, associated with head injury, infection, or delayed secondary hydrops. Ninety per cent of the cases scanned showed dilated vestibular aqueducts, and all cases with progression of the hearing impairment demonstrated this structural abnormality. Approximately one-third of the cases had normal vestibular function, but a further third demonstrated a unilateral peripheral deficit, while the remaining third showed bilateral vestibular hypofunction. There was no intra-familial concordance of vestibular findings, and no correlation between vestibular abnormality and presence or absence of a dilated vestibular aqueduct, with or without a Mondini malformation. In older children and adults, Pendred syndrome was associated with a profound, symmetrical, sensorineural auditory impairment, and a variety of vestibular abnormalities, which are not uniform within families, or correlated with structural labyrinthine deformities.

Tc-99m radiolabelled ciprofloxacin, which we call Infecton, was first described by the radiopharmacist K. Solanki, who noted that the effectiveness of ciprofloxacin diminishes when taken with iron. He postulated that this was because of chelation of the iron with the antibiotic. He, therefore, prophesied that he could chelate technetium-99m to the antibiotic and this would lead to technetium-99m-ciprofloxacin.

The purpose of this study was to evaluate the usefulness of 99mTc labelled ciprofloxacin imaging in detecting the presence of infection in patients with symptomatic knee prostheses. Among 16 randomly selected patients of whom seven had infection based on clinical and microbiological findings and nine did not, 99mTc-ciprofloxacin images were obtained at 1, 4 and 24h after the injection of the tracer. While there was some diffuse non-specific accumulation of 99mTc-ciprofloxacin in large synovial joints and in prosthetic knee joints, the infected knee prostheses were found to show more intensive focal uptake, which also extended outside the synovial cavity. The infection related uptake remained visible in the 24h images, whereas non-specific uptake had a fading tendency at this time point. 99mTc-ciprofloxacin imaging showed diagnostic sensitivity of 86% and a specificity of 78% for correctly classifying the presence of infection. The data indicate that 99mTc-ciprofloxacin imaging may be used in the diagnosis of knee prosthesis infections. Infection-related uptake remains visible in the 24h images and is typically found also outside the synovial cavity, which should be noted in the evaluation of the images.

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.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.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.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.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.(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.

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.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.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 (P0.001). 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.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.

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.

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.

Unlike the majority of imaging modalities used in the management of patients with suspected or proven malignancy, which rely on alterations in structure to visualize the tumour site, nuclear medicine imaging techniques utilize the ability to visualize alterations in metabolism. These alterations in metabolism may occur in the tissues surrounding the tumour site or may occur in the tumour itself. Radiopharmaceuticals used in tumour imaging may also be divided into those that are specifically taken up by tumours and those whose uptake is non-specific. These non-specific agents also localize in other pathological processes such as inflammation. In this chapter, the principles underlying the localization of radiopharmaceuticals used for tumour imaging will be discussed (Table 2.1) and the role of nuclear medicine in the management of cancer patients will be explored.

To evaluate the performance of the 99mTc-labeled monoclonal antibody CYT-351 in visualizing prostate cancer, radioimmunoscintigraphy (RIS) was performed in 35 patients.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.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%.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 cell surface is a complex reflection of the events in its nucleus and cytoplasm. At the same time, the activities of the nucleus and the cytoplasm depend on chemical information transmitted from the cell surface by signal transduction. This interaction results in exploitable differences between the surface properties of a cancer cell and its normal and benign counterparts. Tumour targetting using radiolabeled peptides, monoclonal antibodies and fragments makes use of all of these properties.

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.

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.

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.

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.

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.

The aim of this prospective study was to determine the ability of the captopril renogram to reveal the presence of angiotensin II-dependent renovascular disorder in hypertensive patients with chronic renal failure and to assess the possibility of predicting beneficial effect of angiotensin-converting enzyme (ACE) inhibitors on renal function.Forty-one patients were evaluated. Baseline renal scintigraphy was performed with 80 MBq of 99mTc-mercaptoacetyltriglycine (MAG3) injected intravenously. Scintigraphy was repeated within a week with 25 mg of oral captopril given 60 min prior to the test. Using the measurements outlined by the Working Party on Diagnostic Criteria of Renovascular Hypertension with Captopril Renography, the patients were categorized into high (7 patients), indeterminate (19 patients) and low (15 patients) probability for renal artery stenosis (RAS).In five of the seven patients with high probability, the presence of RAS was confirmed angiographically and corrective surgical procedure performed in two. In patients with GFR of 10 ml/min/1.73 m2 and/or split renal function of 10% or less, all qualitative and semiquantitative scintigraphic parameters were nonspecific. Mean parenchymal transit time of tracer was a useful parameter to predict the beneficial effect of ACE inhibition therapy in 23 patients (14 low and 9 indeterminate probability of RAS).In hypertensive patients with renal failure, captopril renal scintigraphy can be utilized to identify the presence of angiotensin II-dependent renal dysfunction and possibly help to predict the beneficial effect of ACE inhibitor therapy.

The specificity of nuclear medicine techniques for imaging cancer is improved by characterization of the cancer cell as different from the normal. Radioimmunoscintigraphy, imaging with radiolabelled antibodies and radioimmunotherapy, using beta emitting radionuclides, are developing to give specific cancer identification and treatment. The new approaches include genetic engineering of humanized antibody constructs for imaging and bifunctional antibody like molecules for a two stage approach to radioimmunotherapy. There is an important clinical role for current radioimmunoscintigraphy with 99Tcm Technetium as the signal.

This is a preliminary study of the parameter, renal output efficiency (ROE), for the quantitation of furosemide (frusemide) response in diuresis renography. This is calculated by a technique independent of variations in uptake rate by the kidneys. Eleven healthy volunteers and 34 patients suspected of upper urinary obstruction were subjected to gamma camera studies using 99mTc-MAG3 and a standard protocol. Furosemide was given at 18 min after the study was started. The ROE was calculated in each kidney and the results were correlated with final diagnosis. The range of ROE in healthy individuals varied between 82% and 98% (mean = 91.6%); while obstructed kidneys showed significantly reduced values (p0.001) ranging between 30% and 76% (mean = 56%). In the diagnosis of urinary obstruction, the ROE has a sensitivity of 91%, specificity of 94% and accuracy of 94%. ROE complements conventional diuresis renography and provides better diagnostic yield in patients with impaired renal function.

As alternatives to anionically transported hippuran, structure distribution experiments on a series of 99mTc-labelled primary substituted ethylene diamine compounds led to selection of 99mTc diaminocyclohexane (DACH) for clinical evaluation, 99mTc DACH, a cation with the structure trans-[O2(DACH)2 99mTc]+ is prepared by mixing 50 mumol DACH, 1 mumol stannous tartrate and 500 MBq of 99mTc. Seven normal volunteers underwent renal imaging and clearance studies using 150 MBq of 99mTc DACH and 1 MBq of 125I hippuran simultaneously. The images with 99mTc DACH revealed good uptake and excretion. The mean +/- 2 SD values of parenchymal and whole-kidney transit time indices and mean parenchymal transit time were 46 +/- 33, 75 +/- 64 and 141 +/- 51 s, respectively, similar to mercaptoacetyl triglycine. The mean clearance of 99mTc DACH was found to be 163 ml/min (SD = 32). Following cationic blockade with 900 mg oral thiamine, significant reduction (p0.001) in DACH clearance was noted, but hippuran clearance remained unaltered. The results support the hypothesis that 99mTc DACH is transported cationically.

The possible contribution of an inflammatory component in osteoarthritis was investigated. There was no correlation between the percentage uptakes of 99Tcm-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells and 99Tcm-methylene diphosphonate (MDP) and between the former and pain scores. A significant correlation was found between the percentage uptake of 99Tcm-MDP and pain scores (0.002P0.01). In osteoarthritis, 99Tcm-HMPAO-labelled white cell imaging may or may not show a positive localization in the synovial membrane. Positive white cell localization appears to be limited to the area that corresponds to the radiological evidence of the condition and the positive uptake of the skeletal imaging agent.

Octreotide is a synthetic analog of the peptide hormone somatostatin (SMS). A wide variety of tumors express enhanced numbers of SMS receptors, notably neuroendocrine tumors and lymphomas, but also some of the more common adenocarcinomas. Octreotide contains only eight amino acids, some of which are in the (D) configuration in order to enhance the stability of the molecule in vivo. Tyrosine and DTPA-containing analogs of octreotide have been synthesized and labeled with iodine-123 and indium-111, respectively, with the intention of targeting SMS receptor-containing tumors for diagnostic purposes. Both radiopharmaceuticals demonstrate a high sensitivity and specificity for these tumors, indicating a clinical role for these agents in management of these diseases. Lessons can be learned from the success of these agents when designing improved antibody-based molecules. Tumor uptake of radiolabeled octreotide is very rapid, occurring within minutes of administration. Blood clearance is also rapid, such that tumors are soon visible even in areas of high blood background. An interesting finding has been the differences between the pharmacokinetics of the iodinated and indium-labeled species. Although the majority of 123I-Tyr3-octreotide undergoes hepatobiliary excretion, 111In-DTPAPhe1-octreotide is eliminated predominantly by the kidneys. These results suggest that the smallest possible antibody-like tracers are likely to have advantages over native immunoglobulins and conventional Fab-like fragments.

A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We compared an 123I-labeled somatostatin analog Tyr-3-octreotide (TOCT) and 123I-labeled metaiodobenzylguanidine (MIBG) scintigraphy in seven patients with histologically proven metastatic carcinoid tumors. The optimum time for identifying tumor uptake on scanning after [123I]MIBG was 24-48 hr, and after 123I-TOCT 10-30 min postinjection. Both radiopharmaceuticals showed a varying spectrum of tracer uptake ([123I]MIBG showed no uptake in one patient; minimal in two; moderate in two; and intense in two; 123I-TOCT showed no uptake in two patients; minimal uptake in one; moderate uptake in two; and intense uptake in two). In two patients, 123I-TOCT identified metastatic lesions not seen by [123I]MIBG scintigraphy. These preliminary results suggest that [123I]MIBG and 123I-TOCT are useful and complementary imaging techniques for detecting metastatic carcinoid tumors.