Search

Objectives: Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation., Methods: Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection. Discrepancies between the results of plasma clearance and urinary clearance assessments were investigated by using an uncollimated gamma camera to measure the total retention of the tracer., Results: Conventional slope-intercept calculations overestimated clearance compared with the new technique by more than 20% in 21% of the patients. Significant differences between the results of the two methods were more likely in patients with more severe ascites. Results of urine collection-based measurements of Cr-51 EDTA clearance were frequently significantly lower than measurements using the new technique, whereas measurements of urinary clearance of creatinine were higher. Gamma camera measurements suggest that discrepancies between total and urinary clearance of Cr-51 EDTA are due to incomplete urine collection., Conclusion: The new technique is a practical method for assessment of kidney function and should be used in patients with liver disease who have or may have ascites.

Aim: The aim of this study was to identify a practical sampling regimen and calculation method that could be used to measure the glomerular filtration rate in patients with ascites using plasma sampling., Patients and Methods: Thirteen potential liver transplant patients with cirrhosis and ascites were injected with Cr-51 ethylenediaminetetraacetic acid, and plasma samples were obtained at up to 16 time points for each patient. Reference clearance values were calculated using the area under the plasma clearance curve, which was calculated using all the available data points. Clearance calculations were then performed using three and four data points from each patient and three different calculation methods to identify a sampling regimen and calculation method that yielded good agreement with the reference values., Results: The reference clearances ranged from 6 to 80 ml/min. Sampling at 2, 4, 8 and 24 h and calculation of the area under the plasma clearance curve using a log-linear trapezoidal rule with extrapolation to zero and infinity yielded a relative root mean square difference from the reference of less than 7%., Conclusion: This method for measuring glomerular filtration rate in patients with cirrhosis and ascites was found to be more accurate than the slope-intercept technique and is a practical alternative to urine collection.

Objective: To assess the quality of nuclear medicine reporting, within a private UK hospital, of five physicians from four different National Health Service trusts and compare it with a similar previous clinical governance exercise., Methods: Reports (n=140) were shown anonymously to all five physicians, including the one who produced the report. Each physician ranked them on a scale of 1-5, with 1 and 5 corresponding to complete disagreement and complete agreement, respectively. All reports with at least one score of <4 were subjected to consensus review by all five physicians and subsequently given a consensus score., Results: Six hundred and ninety-one audit opinions were present out of a possible 700 (98.7%). Forty-three reports were reviewed, of which 11 received a consensus score of <4 (7.9%). This is not significantly different from the proportion of nontrivial errors in our earlier study (10.2%). Only three reports were present, however, with a score of <3 (2.1%), significantly fewer (P<0.02) than the proportion of nontrivial errors in our earlier study. No scores of 1 were recorded. No reporter attracted significantly more scores of <4 compared with the overall proportion of such scores. A score given by an auditing physician which was 2 or more points different from the consensus score was defined as a suboptimal audit. Forty-four of 691 suboptimal audits (6.4%) were present, significantly fewer than the proportion of suboptimal audits in our earlier study (9.7%; P<0.03)., Conclusion: Studies such as these provide a useful framework for monitoring performance. This improved significantly in this study as compared with our previous audit.

Objective: To perform a retrospective review of all patients receiving technetium-99m ((99m)Tc)-labelled sulesomab over a 4-year period to determine if soft tissue infections can be accurately identified., Methods and Materials: We reviewed the results of 124 (99m)Tc-sulesomab studies performed over a 4-year period. Of these, 34 were performed for undiagnosed fever in which soft tissue infection was suspected to be the main cause. The patients' clinical notes, microbiology reports and other imaging findings were reviewed to determine the clinical outcome following the scan. The scans were regarded as being true-positives if (i) uptake correlated with the site from which fluid or tissue was obtained and which grew bacteria, and/or (ii) the site of abnormality was reported as having an infection on other imaging or (iii) there was a clinical correlation with the referring clinician's evaluation of the patient. Planar imaging was performed using standard protocols, together with single-photon emission computed tomography (if required) at 1 and 4 h after injection of 20-30 mCi (740-1,110 MBq) (99m)Tc-sulesomab., Results: Three patients were unevaluable. In the remaining 31 patients, 21 (99m)Tc-sulesomab studies were regarded as true-positives and 6 patients had true-negative scans. One patient had a false-positive scan (abnormal uptake with negative microbiology) and 3 had false-negative scans (infection confirmed but a negative scan)., Conclusion: In suspected soft tissue infection, (99m)Tc-sulesomab imaging has a sensitivity of 88% with a specificity of 86% and overall accuracy of 87%. (99m)Tc-sulesomab provides an accurate method of imaging for suspected soft tissue infection, which is also fast and convenient, as cell labelling is not required., ((c) 2008 S. Karger AG, Basel.)

There is increasing recognition that Henoch-Schonlein purpura may present in an atypical form in which gastrointestinal symptoms may predominate, and classic cutaneous changes may be delayed or absent. This may lead to significant diagnostic delay. We report the case of a 9-year-old girl who presented acutely with life-threatening gastrointestinal haemorrhage from multiple intestinal sites, with no skin rash and only mild evidence of renal involvement. Henoch-Schonlein purpura was confirmed by finding IgA deposition on vessels within gastric and duodenal mucosa, while immunohistochemistry also identified dense focal T cell infiltration in gastric mucosa and within duodenal epithelium. After initial stabilisation, the patient became shocked due to further gastrointestinal haemorrhage. Isotope bleeding scan identified multiple bleeding sites. Her endoscopically confirmed gastritis was sufficiently severe to preclude corticosteroids, and she was thus treated with intravenous immunoglobulin. This therapy induced prompt and sustained resolution of symptoms, and she has remained well since. Our patient's response concords with previous reports in corticosteroid-resistant cases to suggest that severe intestinal Henoch-Schonlein purpura may respond preferentially to intravenous immunoglobulin (IVIG) therapy. In severe cases where there is significant gastritis, IVIG provides an effective alternative to corticosteroids that may be employed as first-line therapy.

Background: The significance of late urinary tract infections (UTIs) after renal transplantation and their association with scarring and graft dysfunction remains controversial. We sought to define the prevalence of renal scarring in allograft recipients with a history of late recurrent UTIs, to determine whether the presence of vesicoureteric reflux (VUR) confers an increased risk of scarring and to establish whether scarring correlates with graft dysfunction., Methods: Among 307 renal allograft recipients, we identified 56 (18%) with late recurrent UTIs (> or =3/year). A total of 32 patients had undergone further investigation by both 2,3 dimercapto-succinic acid single-photon emission computed tomography (99mTc-DMSA SPECT) scan and micturating cystourethrogram (MCUG)., Results: Of the 32 patients, 24 (75%) had scars on 99mTc-DMSA SPECT and 15 (47%) had reflux on MCUG. Thirteen of these 15 patients with reflux (87%) had scars, although there was no significant correlation between number of scars and degree of reflux. Eleven of 17 patients (65%) with UTIs but without VUR had scars, as did 12 of 14 (86%) with previous graft pyelonephritis. The pattern of scarring (typically multiple focal cortical defects) suggested infection as the cause. This pattern was not seen in a contemporary cohort with vascular occlusions and was rarely seen in patients with chronic allograft nephropathy. Scarring was not associated with inferior graft survival (median follow-up, 15 years)., Conclusions: In patients with late UTIs, renal scarring is a frequent finding. Scarring may occur even in asymptomatic patients without VUR. The lack of an effect on graft survival may reflect successful intervention with prophylactic antibiotics and surveillance urine cultures. Late recurrent UTIs may be damaging to renal allografts, even in the absence of reflux.

A 34-year old lady had a (67)Gallium citrate scan and demonstrated uptake by both of her breasts--diffuse in the right breast, but focal in the left breast at the "9 o'clock position". Core biopsy from both breasts showed fibroadenoma and no malignant cells were found. Though uptake of (67)Gallium citrate is normally associated with malignancy or infection there may be other causes of uptake and follow-up biopsy should be performed.

Evidence for the cost effectiveness of PET/CT imaging is now driving the widespread introduction of PET/CT services throughout the UK. The provision of PET/CT facilities will require a workforce of medical, scientific, technical and engineering staff who are adequately trained and fit for purpose. Suitably trained staff in this speciality are scarce. The development and accreditation of training courses and other educational resources for training programmes in all disciplines will therefore be required at a national and regional level. The implementation of PET/CT training can be achieved more cost-effectively by developing multi-professional learning resources whenever possible. It is intended that the recommendations would be implemented by close co-operation of both public and private healthcare providers together with educational establishments.

Background: meta-[131I]Iodobenzylguanidine (131I-MIBG) has been used to treat patients with disseminated neuroendocrine tumours (NET). However, so far there is limited information related to the efficacy of this agent beyond the normal 6-month assessment period. Before we can assume that such treatment would be beneficial to patients with these tumours the outcome of the patients over a longer time course should be determined. In many centres financial or radiation protection constraints mean that lower activities of 131I-MIBG have to be used at each administration, therefore instead of giving a single administration of a higher activity 131I-MIBG a series of multiple lower activity administrations are used., Methods: The case records of 25 patients who had received 131I-MIBG over a 4-year period, from 1 June 1997 to 30 June 2001, were reviewed. Overall time of clinical follow-up range from 1 to 60 months, with a mean of 16 months). There were 16 female and nine male patients (mean age 55.6 years; range, 30-79 years). Most of patients had carcinoid (17), two had phaeochromocytoma, two gastrinoma and two an undifferentiated NET, one had malignant paraganglioma and one had medullary cell carcinoma of the thyroid. All had avid uptake for 123I-MIBG on diagnostic scanning. The minimum number of treatments received was 1 in 4 patients (with activities of 2.0 to 3.4 GBq); the maximum was 11 treatments (with cumulative activities as high as 29.1 GBq). Treatment was given using an infusion pump and was normally repeated at 12- to 16-week intervals (mean number of treatments per patient, 4). Response to therapy was determined by changes in the size of the tumour on computed tomography and/or magnetic resonance imaging using the response evaluation criteria in solid tumours (RECIST). Toxicity was measured using blood and urine tests of renal, hepatic, thyroid and bone marrow function. The median time from the last treatment to progression of disease and death (if applicable) was also calculated., Results: No significant or long-lasting toxicity was encountered. At 6 months after the patient's last treatment, 18 patients (72%) had no evidence for progression. Twelve months after their last treatment 12 (48%) patients had no evidence for progression. At 18 months after the patient's last treatment, only seven patients (28%) had no progression of their disease. Overall, the median progression-free survival was 15 months. In those patients with stability or response at 6 months there was a prolonged progression-free survival and overall survival. In those with progression of disease at 6 months, at the 6-month assessment point, there had been four deaths (16%), at 12 months, there were three additional cancer deaths and finally at 18 months, there were a further five deaths. The median survival was 18 months. In those patients who died the mean time interval between disease progression and death was 4.6 months (range 0-12 months)., Conclusion: Of the patients treated with low-activity 131I-MIBG 68% had significant benefit for at least 6 months post-treatment. In these patients with progressive and extensive disease this technique provided prolonged progression-free and overall survival with minimal side effects especially if an initial response to treatment was seen.

Background: The aim of the study was to determine the value of radioisotope bone scans in the preoperative staging of patients with hepatopancreatobiliary (HPB) cancer., Methods: Bone scanning was performed as part of a routine staging protocol in 402 consecutive patients with HPB cancer over a period of 5 years. Patients with positive bone scans underwent coned radiography, computed tomography with review on bone windows, or a bone biopsy. Bone scans were reviewed along with staging investigations, surgical and histological findings. Patients were followed for a minimum of 6 months., Results: There were 171 patients with colorectal liver metastases, 106 with suspected pancreatic cancer, 47 with hepatocellular cancer, 52 with gallbladder cancer or cholangiocarcinoma, and 26 with other types of HPB cancer. Bone scans were negative in 377 patients (93.8 per cent) and positive in 25 patients (6.2 per cent). Of the 25 positive scans, 16 were falsely positive as a result of degenerative bone disease. Of nine patients with a true-positive bone scan, four had locally irresectable disease and four distant metastases. In only one patient did the bone scan result alone influence the decision to resect the HPB cancer. Overall sensitivity was 100 per cent, specificity 95.9 per cent, positive predictive value 36.0 per cent and negative predictive value 100 per cent., Conclusion: Bone scanning should not be included in the routine staging protocol for HPB cancer.

(123)I mIBG (meta-iodobenzylguanidine) and (111)In pentetreotide scintigraphy imaging modalities are useful in demonstrating neuroendocrine tumours. Although (111)In pentetreotide is generally held to be a more superior imaging agent than (123)I mIBG for neuroendocrine tumours, we noted a differential uptake of the two agents by different tumour sites within individual patients. In some cases, the two tracers appeared to demonstrate different lesions within the same patient. The aim of this study wasto determine the positivity of the two imaging modalities, the degree of correlation between them and to highlight any clinically useful differences between the two modalities. (123)I mIBG and (111)In pentetreotide images of 149 consecutive, biopsy-proven or biochemically confirmed, neuroendocrine tumour patients were compared. All the patients underwent whole-body imaging and upper abdominal single-photon emission computed tomography (SPECT). The results of both types of imaging were compared, lesion by lesion, for each individual patient. The overall positivity rate for (111)In pentetreotide was 79%, and that for (123)I mIBG was 63%. When both agents were positive, the (111)In pentetreotide highlighted more lesions within the same patient in 33%, whilst the (123)I mIBG highlighted more lesions in 13%. In 12% of patients both agents were positive, but different lesions were seen with the two agents. (111)In pentetreotide has greater positivity than (123)I mIBG for imaging neuroendocrine tumours. However, the two modalities can highlight different tumour lesions, suggesting the presence of phenotypically diverse tumour populations within individual patients. These findings are likely to influence clinical management in the future.

Background: Functional and anatomical imaging methods are currently the standard approach to the evaluation of carcinoid tumor extent. Due to the nature of carcinoid tumors ,there is not a single imaging procedure that is sufficient to detect the malignancy. The aim of the study was to compare the value of CT, MR and functional imaging study with(111) In-Octreotide (SRS) in carcinoid detection and evaluation of its extent as well as to work out the imaging studies diagnostic algorithm that could enhance diagnostic efficacy., Material/methods: A total of 34 patients with carcinoid tumor confirmed clinically,biochemically and/or histopathologically were enrolled into the study. Computed tomography (CT) examinations of the abdomen and pelvis were performed before and after administration of a contrast medium, the triple-phase liver scanning included. Magnetic Resonance Imaging (MRI)of the liver was performed according to the standardized protocol before and after administration of a contrast medium .Planar scintigraphy with(111) In Octreotide and SPECT were performed. In each case liver as well as lymph node metastases in the abdomen and pelvis were searched for. All results were reviewed independently. Clinical picture at follow-up and further imaging and/or histological studies confirmed or excluded the diagnosis of the disease., Results: Twenty nine patients were diagnosed with carcinoid tumor. Liver metastases were found in 26 patients and lymph node metastases were detected in 18 of them. Complete diagnostic conformity as far as the diagnosis and extent of the disease are concerned was obtained only in 7 cases. Incorrect assessment of the disease extent was the source of discrepancy between the imaging studies results in most of the remaining 22 patients. The SRS and MR results of liver metastases detection were mostly consistent with one another. Both imaging modalities evaluated the extent of hepatic metastases incorrectly in 22%of the patients,as compared to 43% of the patients for CT. The highest proportion percentages of incorrect results of lymphatic involvement detection were 41%, 29%and 43%for MR, SRS and CT, respectively., Conclusions: The results of our study have indicated that application of a complex imaging algorithm enables higher accuracy of hepatic and lymph nodes metastases detection in carcinoid tumor patients. Combining the results of MR and SRS in evaluating the extent of the carcinoid disease seems to represent higher diagnostic value than relying on one of this method in combination with CT images.

The quantification of the tumour volume is essential for the assessment of therapy-induced changes. Traditional methods of assessing the response of neuroendocrine tumours using radiological methods yield poor results, particularly within the liver. The aim of this study was to establish whether it would be possible to identify a method using functional volumes to predict the response of tumours to various therapies. Twenty-two patients with neuroendocrine tumours of carcinoid type in the liver were treated with chemotherapy, chemo-embolization or 90Y-radiolabelled somatostatin analogues. All patients underwent 111In-pentetreotide single-photon emission computed tomography (SPECT) and computed tomography (CT) scan pre- and post-treatment. The tumour functional volume, a measure of metabolically active tumour tissue, was calculated from the SPECT images using a 10-point display; regions of interest were drawn around 50% of the maximum tumour activity, slice by slice, and then multiplied by the slice thickness (9.3 mm). Any difference in functional volume was compared with the CT response, using the Response Evaluation Criteria in Solid Tumours (RECIST), and clinical outcome. At 6 months after treatment, 14 patients showed a good clinical response, as measured by a reduction in pain, flushing or abdominal symptoms; the functional volume of the tumours in these patients decreased by a mean of 25% (range, 1-52%). Of the eight patients who showed no symptomatic relief, or in whom symptoms worsened, the functional volume increased by a mean of 74%. Using a change in functional volume of more than 25% as significant, SPECT predicted 13 of the 22 (59%) clinical outcomes correctly; if a 10% change was used, 18 of the 22 (81.1%) clinical outcomes were correctly predicted. However, CT, using RECIST, only predicted eight of the 22 (36%) clinical outcomes correctly. The assessment of the total functional volume by SPECT quantification is more useful than CT in monitoring tumour response after treatment, and the changes in functional volumes after therapy correlate well with the clinical response.

Background and Aim: Clinical governance is important. Clinical audit is part of clinical governance. The aim of this study was to perform a clinical governance exercise, and the reporting arrangements at an independent hospital provided the opportunity to do this over two phases between 1999 and 2002. Six physicians from four different UK National Health Service (NHS) trusts participated., Methods: Reports were shown anonymously to between two and five of the physicians who had not produced the report. Reports with at least one disagreement were reviewed by the group in order to reach concensus as to whether the disagreement was non-sustainable (NS), trivial (T) or non-trivial (NT), the last two, respectively, judged to make an insignificant or potentially significant impact on patient management., Results: In phase 1,239 audits were produced on 83 reports (2.9 per report), and in phase 2, 636 on 137 reports (4.6 per report). In phase 1, 14 (17%) reports attracted at least one disagreement (NS, five; T, four; NT, five). Of 239 audits, there were 20 disagreements of which five were NS. Moreover, nine audits agreed with a report with a NT disagreement, giving 14 suboptimal audits (5.9%). In phase 2, 80 (58%) reports attracted at least one disagreement (NS, 31 (P<0.003 vs phase 1); T, 35 (P<0.001); NT, 14 (P>0.05)). Of 636 audits, there were 153 disagreements, of which 37 were NS (P<0.05 vs phase 1). Twenty-five audits agreed with a report with a NT disagreement, giving 62 suboptimal audits (9.7%) (P>0.05). Overall, 19/220 reports (8.6%) were thought NT, an error rate comparable to reporting elsewhere in radiology. After phase 1, auditors became more aggressive but the quality of auditing tended to decline, as did the quality of reporting (although not significantly)., Conclusion: This study provides a useful framework for monitoring performance.

Objectives and Design: Scintimammography using Tc-99m MIBI is becoming established as a second line diagnostic test for the detection of breast cancer in patients with suspected primary disease. Though most published clinical studies compare scintimammography (SMM) with mammography (XMM), in clinical practice they are likely to be used sequentially with the scintimammography following the mammography., Materials and Methods: To determine the possible accuracy of such an approach, receiver operator characteristic (ROC) curves were produced for SMM, XMM and a combination of both studies performed over 2 years period on 162 suspicious lesions in 154 patients with no previous history of breast cancer. Each scan was reported in 5 grades: 1-normal or definitely benign; 2-possibly normal or possibly benign; 3-equivoval; 4-probably cancer; 5-definitely cancer. The results have been verified by pathological examination of biopsy material obtained from each suspicious mass., Results: There were 102 malignant breast tumours and 60 non-malignant breast lesions. SMM correctly diagnosed 89 breast cancers, and was false negative in 13 cases. It was true negative in 36 benign breast lesions. The sensitivity of SMM was 87%, specificity 65%, PPV 81% and NPV 75%. XMM diagnosed correctly 70 malignant tumours. The sensitivity, specificity, PPV and NPV for XMM were respectively: 69%, 72%, PPV 81% and NPV 57%. However, if a combination of the two methods is used the overall diagnostic accuracy was as follows: 92%, 80%, 89% and 86%. Evaluation of index area under ROC curve allows in both diagnostic methods XMM and SMM results as follows: 0.79 and 0.83. Additional sequence imaging allows 0.94. Combined XMM and SMM in suspected primary breast cancer patients has higher diagnostic accuracy than each method separately (p < 0.05)., Conclusion: This study shows that the combination of mammography and scintimammography produces more accurate results than either modality alone this is how these test should be performed in clinical practice.

Objectives: Although it only occurs in a minority of patients, renal involvement is a life-threatening complication of scleroderma (SSc). We have investigated the utility of two formulae to calculate glomerular filtration rate (GFR) in a population of SSc patients., Methods: Twenty-six patients (20 female, 6 male, median age 58 yr, age range 12-80 yr) satisfied our criteria for inclusion in a retrospective comparison of measured and calculated GFR. GFR was measured using (51)Cr-EDTA. The modified Cockcroft and Gault formula and equation 7 from the Modification of Diet in Renal Disease (MDRD) were used to calculate GFR., Results: Eighteen out of 19 patients analysed with a serum creatinine concentration less than the upper limit of the normal range had a measured GFR outside the normal range. Three patients with a normal creatinine concentration had a measured GFR <60 ml/min and in each of these the calculated GFR was also abnormal. All patients with a measured GFR <60 ml/min were identified using both the MDRD and the modified Cockcroft and Gault formula to calculate GFR. The greatest correlation between measured and calculated GFR was seen when the MDRD formula, which employs demographic and serum variables, was used in patients with body surface area (BSA) >1.4 m(2) who were not taking Iloprost (r=0.91). Use of the Cockcroft and Gault formula to calculate creatinine clearance with a correction factor for GFR, the inclusion of patients taking Iloprost and the inclusion of patients with BSA <1.4 m(2) were all associated with a lower degree of correlation., Conclusion: Serum creatinine is a poor marker of renal function in SSc patients. Calculating GFR from demographic and serum variables is a simple technique to identify SSc patients who have abnormal renal function. The authors recommend the use of the MDRD formula.

Unlabelled: High-activity (111)In-pentetreotide has been used to treat patients with disseminated neuroendocrine tumors. There is, however, little information related to the efficacy of this agent beyond the normal 6-mo assessment period. Before we can assume that such treatment would be beneficial to patients with neuroendocrine tumors the outcome of the patients over a longer time course should be determined., Methods: The case records of 16 patients who had received high activities of (111)In-pentetreotide (with cumulative activities as high as 36.6 GBq) over a 2.5-y period, from January 1, 1997, to June 30, 2000, were reviewed. There were 8 female and 8 male patients (age range, 32-76 y): 10 patients had carcinoid, 2 had medullary cell carcinoma of the thyroid, and 1 each had a gastrinoma, glucagonoma, fibrolamellar cancer, and malignant histiocytoma. The minimum number of treatments received was 1 in 2 patients (with activities of 3.1 and 7 GBq); the maximum was 10 treatments (total, 36.6 GBq). Treatment was given using an infusion pump and was repeated at 4- to 12-wk intervals (mean number of treatments per patient, 6). Response to therapy was determined by changes in the size of the tumor on CT using the response evaluation criteria in solid tumors. Toxicity was measured using blood and urine tests of renal, hepatic, thyroid, and bone marrow function. The mean and median time from the last treatment to progression of disease and death (if applicable) was also calculated., Results: No significant or long-lasting toxicity was encountered. At 6 mo after the patient's last treatment, 5 patients (30%) had disease progression, 2 had complete responses, and 3 had partial responses. Twelve months after their last treatment, 9 patients (56%) had disease progression, and, at 18 mo, 11 patients (69%) had disease progression. The mean progression-free survival was 12.25 mo (median, 9 mo). For those who survived 6 mo after their last treatment, the mean survival was 15.75 mo (median, 16 mo). At the 6-mo assessment point, there had been 3 deaths (19%): 1 death was not related to cancer. At 12 mo, there was 1 additional cancer death. At 18 mo, there were 3 additional deaths (1 was not related to the patient's carcinoid tumor but was due to a second coexistent cancer). By the end of the 18-mo assessment period, 7 patients (44%) had died. The mean time interval between disease progression and death was 5 mo., Conclusion: In patients treated with high-activity (111)In-pentreotide, 70% had some benefit for at least 6 mo after the end of treatment; however, 31% of patients will have sustained benefit at 18 mo from this treatment. This was obtained without significant toxicity.

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m(-2)x three administrations with a serum carboxypeptidase G2 level of 0.05 U ml(-1). Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems.

Scintimammography with (99m)Tc-MIBI has been shown to be an effective adjunct to imaging of the breast with mammography. Uptake of (99m)Tc-MIBI is particularly high in sites of non-calcified cancer and ductal carcinoma in situ (DCIS), and as a consequence it may be possible to use this method of imaging in identifying multifocal or multicentric disease. The aim of this study was to evaluate the efficacy of preoperative scintimammography in the detection of multifocal and multicentric breast cancer and compare these results with mammography. A retrospective review was performed of 353 women imaged with (99m)Tc-MIBI as part of the clinical assessment of their suspected primary breast cancer. The results of the scintimammography and mammography were then compared with the final pathological diagnosis obtained after mastectomy in all patients. Histopathological assessments of breast tissue from mastectomy confirmed 40 women (12%) had multifocal (34) or multicentric (six) breast cancer. Scintimammography correctly identified 39 of these cancers and the multifocal or multicentric character of the cancer was identified in 22 (52%) of these patients. Anatomical imaging performed in all 40 patients including 25 with mammography alone, mammography and ultrasound in 11 cases and ultrasound alone in four patients. Anatomical imaging identified cancer to be present in 28 patients (70%) and the combination of mammography and ultrasound identified correctly that the cancer was multifocal or multicentric in eight patients (22%). In this study scintimammography was able to identify more cases of multifocal and multicentric cancer than mammography and/or ultrasound. In patients where pre-operative identification of multicentric or multifocal disease can alter treatment scintimammography may be a useful investigative tool.

Objective: To assess the effectiveness of a dual head coincidence gamma camera in identifying ovarian cancer as a less expensive alternative to the traditional 2-[18F] fluoro-2-deoxy-D-glucose (18FDG) system using positron emission tomography., Design: Prospective study., Population: Twenty consecutive women suspected of having ovarian carcinoma. Inclusion was based on abnormal serum CA125 (reference range is 0-35 units/L), ultrasound, computerised tomography or clinical findings., Methods: Women underwent assessment before staging laparotomy. Two nuclear medicine physicians, who were blinded to the pre-operative assessment, reported on 18FDG- dual head coincidence gamma camera imaging., Main Outcome Measures: The histology and operative staging were compared with the 18FDG- dual head coincidence gamma camera findings., Results: Twelve women had pelvic malignancies (nine primary and three recurrences), seven women had benign pathology and one patient had a borderline malignancy. We were able to image accurately all malignant pelvic masses with dual head coincidence gamma camera, as well as accurately demonstrate disease spread. Two of the benign pelvic masses localised 18FDG. The positive predictive value for detecting malignancy was 86%., Conclusions: Dual head coincidence gamma camera offers accurate and affordable imaging in suspected ovarian masses, with improved specificity over CA125, ultrasound and computerised tomography. These results are similar to those obtained on more expensive dedicated PET systems. We report on a series of patients believed to have primary or recurrent carcinoma and recognise the need to include patients more likely to have benign lesions to assess false positive results. However, we believe that dual head coincidence gamma camera is useful in the pre-operative assessment of women with suspected ovarian cancer.

Unlabelled: The aim of this study was to compare the accuracy of 99mTc-methoxyisobutylisonitrile scintimammography (SMM) and conventional mammography in patients presenting with suspected primary breast cancer. Receiver-operating-characteristic (ROC) curve analysis was applied to determine if a combination of x-ray mammography (XMM) and SMM was more accurate than a single test alone., Methods: The results of SMM, XMM, and a combination of both studies performed over a 3-y period on 374 suspicious lesions in 353 patients with no previous history of breast cancer were reviewed. Each scan report was reviewed and graded as follows: grade 1, definitely normal or benign; grade 2, probably normal or benign; grade 3, equivocal; grade 4, probably cancer; and grade 5, definitely cancer. The results were verified by pathologic examination of biopsy material obtained from each suspicious mass. ROC curves were generated from these results., Results: There were 204 malignant breast tumors and 170 nonmalignant breast lesions. SMM diagnosed correctly 181 breast cancers and was true-negative in 122 benign breast lesions: sensitivity, 89%; specificity, 71%; positive predictive value (PPV), 79%; and negative predictive value (NPV), 84%. XMM diagnosed correctly 143 malignant tumors and was true-negative in 117 nonmalignant lesions. The sensitivity, specificity, PPV, and NPV for XMM were 70%, 69%, 73%, and 66%, respectively. Using a combination of the two tests, the combined sensitivity was 93%, specificity was 72%, PPV was 80%, and NPV was 90%. Using the index of the area under the ROC curve obtained by the rating method showed that the combination of XMM and SMM was significantly more accurate than either of the individual tests if performed alone (P < 0.05)., Conclusion: This study shows that the combination of XMM and SMM produces more accurate results than either modality alone. Therefore, if there is doubt about the accuracy of XMM, SMM should be used as the second-line test in breast imaging.

Background: With the increasing demand for breast conservation surgery, the probability of recurrent tumour within the breast increases. Traditionally x-ray mammography (XMM) was used to assess the post-surgical breast, but post-surgery and radiotherapy changes have reduced the accuracy of this method. Scintimammography (SMM) has also been proposed and appears to be more accurate than XMM., Material and Methods: A total of 101 women received (Tc99m) MIBI SMM and 88 had a subsequent XMM. There were 142 sites suspected of loco-regional recurrence breast cancer. During the study the patients did not receive any treatment other then hormonotherapy. SMM was performed by the standard Diggles-Khalkhali method and XMM was performed using standard 2 views. Analysis was performed and the results of each type of imaging compared with histology. In the ROC curve analysis 5 points of certainty were used: from 1 being definitely normal to 5 being definitely cancer; grades 4 and 5 were counted as positive., Results: The overall sensitivity value of SMM was 84% and specificity was 85%, compared with a sensitivity of 52% for XMM and a specificity of 84%. Analysis of areas under ROC curves provides statistically significant difference between SMM and XMM (p < 0.05). Combining the two tests did not significantly improve the diagnostic accuracy of sequence imaging over SMM., Conclusion: ROC curve analysis demonstrates that scintimammography should be the primary investigation in suspected local recurrence following breast conservation surgery.

Background: The diagnostic approach that should be used in disseminated neuroendocrine tumours (NET) remains a significant clinical problem. A novel approach has been the use of 111In Octreotide as functional imaging to find NETs. Therefore, the aim of this retrospective study is to report our comparison with direct CT as standard anatomical imaging., Material and Methods: A total of 48 patients (aged 16-79 years; mean age 55, SD 14 years) were imaged using both techniques with final histological confirmation of NET. Histology was as follows: 26 carcinoids; 2 pheochromocytomas; 4 gastrinomas, 1 islet tumour; 2 paragangliomas, 1 modullary carcinoma of the thyroid, 8 undetermined NET and 4 other tumours with signs of neuro-ectodermal cancers (2 hepatocellular carcinomas (HCC), fibrolamellar HCC and fibrous tumour). All patients had (111)In Octreotide and 30 had (123)I mIBG scans followed by spiral CT with contrast enhancement. 26 patients had single functional scans and 22 had multiple, up to 6 scans. Extent of disease as number of lesions was compared between CT and octreotide., Results: CT was the best modality in 11 patients, in 6 it was as good as (111)In Octreotide. mIBG was the best in 6 patients; in 3 patients mIBG was as good as octreotide study. In 22 patients (111)In Octreotide was the most effective modality. In one patient there was no advantage with any of the tests. Comparison of the number of organs involved indicated that an octreotide study was much more effective than CT scanning (Wilcoxon matched pairs test, p < 0.001) and also the overall number of lesions detected using (111)In Octreotide was greater than with CT (Wilcoxon Matched Pairs test p < 0.01)., Conclusion: Our results confirm the recommendation of the European NET group that functional imaging should be performed in patients with suspected NET.

Objective: This study was undertaken to determine whether preoperative radioimmunoscintigraphy of complex ovarian masses with technetium Tc 99m MAb-170 (Tru-Scint AD; Biomira Inc, Edmonton, Alberta, Canada), a murine whole immunoglobulin G monoclonal antibody that has been found to have panadenocarcinoma affinity, would predict surgical findings., Study Design: The age range of studied patients was 42 to 83 years (mean, 60.3 years). Planar computed tomographic imaging and single-photon emission computed tomographic imaging were performed at 15 minutes, 6 to 8 hours, and 18 to 24 hours after injection of 1000 MBq technetium Tc 99m MAb-170. Laparotomy was performed within 10 days., Results: Eighteen patients had borderline or invasive ovarian cancers verified by histologic examination. All primary malignancies or deposits (including intrahepatic deposits) yielded positive results on radioimmunoscintigraphic imaging. Radioimmunoscintigraphy was able to identify serosal deposits not seen on computed tomographic or ultrasonographic scans. False-positive localization of the antibody was noted in 6 of the 9 patients with benign pathologic processes., Conclusion: It is possible to detect with technetium Tc 99m MAb-170 all patients who have cancer (including sites not seen on computed tomographic or ultrasonographic scan); however, the low specificity (33%) means that patients still require surgical verification of disease.

A prospective trial was performed to assess the accuracy of Tc-99m MIBI scintimammography in 63 women (mean age 65, range 33-85 years) with suspected recurrent breast cancer in the breast and/or loco-regional tissues. All patients had been diagnosed with breast cancer 1-23 years before the scintimammography. A total of 27 breasts had been removed by mastectomy so scintimammography was compared with mammography in the remaining 99 breasts. Pathological follow-up of patients confirmed 33 sites of recurrent disease within the breast, 26 (78%) were identified by scintimammography and 14 (42%) by mammography; 30 (90%) were positive on one test or the other. In addition Tc-99m MIBI scintimammography identified 10/16 (63%) of axillary lymph nodes with recurrent tumour and 4/6 sites of recurrent tumour present elsewhere. Tc-99m MIBI scintimammography is more accurate in identifying recurrent disease in the breast than mammography and can identify loco-regional recurrence outside of the breast.

In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA). Thirty-four patients undergoing surgery for colorectal carcinoma (17 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125I-labeled MFE-23-his scFv (125I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125I-MFE-23-his showed biexponential blood clearance with alpha and beta half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.

Background: The detection of breast cancer relies on physical examination and mammography (XMM). The sensitivity of conventional imaging is lesions-size dependent. However, mammography has good sensitivity in small tumours when microcalcification is present, but the sensitivity is relatively low in other small tumours. The use of scintimammography with Tc-99m sestaMIBI (SMM) may be helpful in this situation. The aim of this study is to compare the diagnostic accuracy of mammography and scintimammography across all groups with different sizes of lesions., Methods: Data for 273 patients aged 26 to 84 years (mean 52; SD 12) with 298 lesions were analysed. All lesions were removed and final histology and pathological size of the tumours were retrospectively reviewed (mean size 2.9 cm, SD 2.4 cm). All patients had XMM and SMM. Each imaging study was graded using five grades of certainty. SMM images were reviewed by an independent specialist blinded to clinical presentation and XMM results. The diagnostic accuracy of each test, overall and by each lesions size subgroup, was compared using receiver operating characteristic curve (ROC) analysis., Results: The sensitivity of scintimammography was consistently high across all size groups; overall 89% (82?100%) compared with 68% (51?88%) for mammography. In those tumours below 2 cm, the area under the ROC was significantly larger with SMM than XMM (p < 0.05), with 80% certainty indicative of greater diagnostic accuracy. Also in all patients the area under the ROC was significantly larger with SMM than XMM (p < 0.05), with 90% certainty indicative of greater diagnostic accuracy. In other groups of lesions size the area under ROC for SMM was larger in lesions size between 2 and 4 cm and slightly smaller in lesions over 4 cm, but it was not significant., Conclusion: Scintimammography using Tc-99m sestaMIBI seems to be a sensitive and consistently reliable diagnostic test for breast cancer independent of the size of the tumour.

Patients with multi-organ disorders may present with a plethora of confusing symptoms and signs. Often early diagnosis of significant disease is essential and can be difficult with standard radiological techniques. This case report presents the use of two radioisotopic techniques to assess brain and lung perfusion in a patient with such an acute-multi-organ disorder-the HELLP syndrome.

Background: Scintimammography using Tc-99m MIBI (SMM) is often used clinically as a second line diagnostic test for the detection of breast cancer in cases where there is concern about the results of x-ray mammography (XMM) and ultrasound. Both of these methods, but particularly XMM, may miss a significant proportion of ductal carcinoma in situ (DCIS)., Material and Methods: This study was performed to determine the possible accuracy of SMM in finding DCIS and comparing this with the accuracy of XMM in the same patient. Over a 3 year period 353 patients with no previous history of breast cancer were imaged with both XMM and SMM. The histology of any suspect area was verified by pathological examination of biopsy material. There were 203 malignant breast tumours., Results: In those 203 cancers there were 15 pure DCIS cancers. SMM correctly diagnosed 12 of these (sensitivity was 80%). XMM diagnosed correctly 8 DCIS (sensitivity 53%) and was equivocal in 2. Combining of both SMM and XMM provided the best result with all but one DCIS identified (sensitivity 93%)., Conclusions: This study shows that the SMM is helpful in detecting DCIS in those cases where XMM failed to detect DCIS or was equivocal. The combination of the two techniques produces a higher sensitivity result than either modality alone.

Purpose: Patients undergoing long-term renal replacement therapy (such as dialysis) have an increased risk for significant cognitive impairment, which may result in memory problems and subsequently missed attendance at dialysis. The aim of this study was to try to identify any abnormalities of cerebral perfusion that could explain a patient's cognitive impairment and to determine if the pattern of these abnormalities would suggest a cause., Materials and Methods: 17 patients (13 men; mean age, 60 years; age range, 29-74 years) in end-stage renal failure or on dialysis had SPECT imaging 10 minutes after injection of 550 MBq (15 mCi) Tc-99m HMPAO. Two of the patients had a history of previous stroke. Other risk factors for stroke were noted in most of the patients (hypertension in 10 patients, smoking or former smoking in 10 patients, and cardiac atherosclerosis in 7 patients). In all patients, attenuation correction was applied and the images were reconstructed into three sets of orthogonal slices. Activity in the frontal and temporal lobes was compared by quantification against the ipsilateral and contralateral cerebellum., Results: Discrete cortical defects consistent with infarcts were seen in 14 patients. The mean right and left frontal-to-cerebellar ratio was 0.837 (SD, 0.09) and 0.837 (SD, 0.08), respectively. This was not significantly different from the right and left temporal-to-cerebellar ratios of 0.843 (SD, 0.07) and 0.848 (SD, 0.07), respectively. Both were within normally accepted ranges., Conclusions: Patients in end-stage renal failure who also had cognitive impairment appear to have a high number of cortical defects consistent with infarcts (suggesting a multiple-infarct type of dementia). There was no evidence of Alzheimer-type dementia.

Unlabelled: The purpose of this retrospective study was assessment of correlation between Tc-99m sestaMIBI uptake and some prognostic factors of breast cancer. The following prognostic factors have been included in this study: size of the tumour, age of the patients, axilla node involvement, oestrogen and progesterone receptor (ER, PR) status, grading system of Bloom-Richardson and Ki-67 antigen expression., Methods: 79 patients were enrolled in this study, with 85 lesions confirmed as primary breast cancers. Mean age of patients was 53 years. Scintimammography (SMM) was performed after intravenous injection of 740MBq. At 5-10 min after injection standard planar images were obtained in prone lateral and anterior supine views. Assessment of correlation between known prognostic factors of breast cancer and uptake of MIBI (evaluated as a tumour to background ratio-TBR) was performed used non-parametric (Kendall-tau correlation) statistical analysis., Results: There were 85 breast cancers (73 invasive ductal carcinomas, 11 DCIS (ductal carcinoma in situ) and 1 lobular carcinoma. There was positive correlation between TBR Tc-99m MIBI uptake and size of the tumour (t = 0.19, p = 0.01), presence of axilla node involvement (t = 0.2, p = 0.006) and also grade of the IDC tumours evaluated using Bloom-Richardson's criteria (t = 0.18, 0.03). There were negative correlation between TBR and presence of PR (t = -0.16, p = 0.02) and borderline negative correlation between TBR and age of patients (t = -0.137, p = 0.06) and also TBR and ER status (t = -0.135, p = 0.065). Patients who are younger and/or have PR or ER negative cancers have higher Tc-99m MIBI uptake. Patients who presented with high grade of malignancy (B-R) also have higher uptake of radiotracer. Also those with higher uptake of radiotracer often had axillary node involvement. This would suggest that more aggressive tumours have higher uptake of Tc-99m MIBI. Finally this study suggest correlation between in vivo uptake of MIBI and some of the known prognostic factors of breast cancer.

Comprehensive evaluation of renal transplants has been important in differential diagnosis of medical and surgical complications in the early post-transplantation period and in the long-term follow-up. If performed well, it yields excellent functional and good anatomic information about the graft that can be effectively used in the patient. That includes selection of patients for biopsy and for various drug regimens. This is true especially in patients with anuric acute tubular necrosis (ATN) and in patients with developing chronic rejection. Improving indices of renal function (effective renal plasma flow, uptake of tubular tracers) can indicate resolution of tubular injury (ATN) while there is still no improvement in plasma creatinine. In patients with chronic rejection, plasma creatinine increases only after approximately 30% of renal function is lost due to graft fibrosis. Early recognition of this condition could permit treatment and delay of retransplantation. The protocol recommended at the Copenhagen meeting includes a flow study, scintigram of the kidneys, prevoid and postvoid bladder image, injection site image (quality control), time/activity curves of the graft and bladder, and quantitative data of perfusion, function, and tracer transit. The flow study obtained during the initial transit of the bolus through the graft could be performed either with 99mTc mercaptoacetyltriglycine, or 99mTc diethylenetriaminepentaacetate (DTPA). Quantitative analysis of perfusion facilitates interpretation of the study during the early post-transplantation period. ATN, common in cadaver transplants, typically shows adequate perfusion. The function phase should include images and time/activity curves. Images alone are insufficient. Quantitative data such as clearance or other indices of function and indices of tracer transit are essential for correct interpretation of the results. Normal images and normal graft function reliably exclude clinically important complications. A single scintigram demonstrating prolonged tracer transit with decreased function cannot separate acute rejection and ATN. On serial studies, decline in function and poor perfusion are indicative of acute rejection. A normally appearing scintigram without cortical retention, but with low function, is consistent with chronic rejection. Pharmacological intervention to exclude obstruction (diuretic renogram) or hemodynamically significant renal artery stenosis (angiotensin converting enzyme challenge) should be used whenever indicated.