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Objectives: Inconsistency in the intercentre measurement of whole kidney mean transit time (MTT) has been reported in a previously published UK audit. The main objectives of this study were to identify a probable value of MTT for each kidney in the UK audit data and to find likely reasons for the reported variations., Methods: Datasets of MTT values were obtained by an independent review of the audit data by four experienced practitioners of deconvolution techniques. The deconvolution techniques used included the matrix method, a constrained least squares method as well as a residence time technique. The datasets were compared using t-test, linear regression, and mean difference analysis., Results: Twelve of a total of 13 datasets showed nonsignificant differences using a paired t-test (P>0.05). For each kidney (x), a collective mean and standard deviation, Mx and SDx, respectively, were calculated from these 12 datasets and a probable range was defined as Mx+/-3SDx. Average SDx/Mx was 3.6% (range 1.5-7.7%). For five kidneys, Mx exceeded the median of the audit results by 3.5-15.3 SDx (P<0.001)., Conclusion: Probable ranges for whole kidney MTT have been estimated with good precision. Underestimation of the area under the plateau of the renal retention function as well as overestimation of the plateau height might have contributed to an underestimation of MTT apparent in some audit results. Visual display of both the renal retention function and the reconvolution curve are suggested as simple quality control measures for analysis software.

Unlabelled: One of the potential limitations in the usefulness of both renal output efficiency (ROE) and normalized residual activity (NORA) is their residual dependence on total renal function. The purpose of this study was to present and examine a new quantitative method whereby the effects of this dependence may be removed., Methods: The analytic method involves the determination of a retention function using an unconstrained matrix algorithm deconvolution technique followed by reconvolution with a chosen standard input function to yield a new secondary renal activity time (A/T) curve from which normalized values of ROE and NORA, denoted as N&#95;ROE and N&#95;NORA, respectively, can then be obtained using conventional definitions. The method has been applied in a series of 50 patient studies, which had been acquired using (99m)Tc-mercaptoacetyltriglycine (99(m)Tc-MAG3) and a standard F+18 furosemide protocol, with values of the ratio of plasma clearance to plasma volume (C/V) in the range 0.013-0.242 min(-1)., Results: Pre- and postnormalization values of NORA, calculated at 30 min after injection, showed a significant difference in mean values (paired t test; P < 0.001), with a maximum observed difference, DeltaNORA(30), of -4.82 (-482%) and with a SD on the paired differences, DeltaNORA(30), of 0.56 (56%) or 0.63 (63%) if background subtraction on the input function (BSIF) had been performed. In contrast, corresponding values of ROE showed a nonsignificant difference in means (P > 0.05) and a SD on the paired differences, DeltaROE(30), of 3.7% or 3.2% with and without BSIF, respectively. The normalized parameters N&#95;ROE and N&#95;NORA were found to be strongly linearly correlated (r = -0.99; P < 0.001), in agreement with theoretical predictions., Conclusion: These results suggest that renal function affects NORA significantly more than ROE. The effects can be corrected by our normalization technique, resulting in equivalent values of normalized ROE and normalized NORA.

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

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

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

The aim of this study was to compare a simple measure obtained visually from serial images, the corticopelvic transfer index (CPI), with renal transit times obtained by deconvolution. The CPI was defined as the time interval between the appearance of the tracer in the renal cortex to its appearance in the renal pelvis. Four groups of subjects as determined by clinical data and renal transit times were investigated retrospectively: 86 normal kidneys, 20 kidneys with renovascular disorder, 17 kidneys with obstructive nephropathy and 26 kidneys with dilated pelves without obstructive nephropathy. There were good correlations only between the CPI and mean parenchymal transit time (MPTT; r = 0.6) and the whole kidney transit time index (WKTTI; r = 0.8). It was concluded that in centres where gamma-camera studies with deconvolution analysis are not possible, the CPI could be a useful parameter in renal radionuclide scintigraphy for suspected renovascular disorders.

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

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.

Ten patients were studied prospectively afer severe closed head injury to determine the relationship between long-term clinical outcome and abnormalities detected by single photon emission tomography (99Tcm-HMPAO SPET), CT and MRI obtained within 60 days of injury. The ability of SPET to detect abnormalities not visualized by CT or MRI after cerebral trauma by the results of this study. Changes detected by SPET [global cerebral blood flow (gCBF) and number of regional cerebral blood flow (rCBF) deficits] soon after trauma were shown to be more closely correlated with long-term outcome than changes detected by MRI or CT. Templates were used to classify lesions by site and a multivariate analysis was undertaken to establish the importance of defect position in predicting clinical outcome. The results suggest that lesions in the temporal lobes, frontal lobes and basal ganglia are related to poor prognosis, and that SPET yields more useful prognostic data than the other methods.

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 (p < 0.001) 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 (p < 0.001) in DACH clearance was noted, but hippuran clearance remained unaltered. The results support the hypothesis that 99mTc DACH is transported cationically.

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.

After closed head injury nineteen patients had single photon emission tomography (SPECT) using the lipophilic tracer 99m-Technetium hexamethyl-propylene-amineoxime (HMPAO) to compare the defects shown by CT and MRI. SPECT showed more focal cerebral lesions than either CT or MRI alone or in combination. Most lesions shown by SPECT were not shown by CT or MRI in the corresponding anatomical regions. The most severely disabled patients showed the highest number of SPECT lesions (average four per patient) and the lowest (mean, SE) cerebral blood flow (718, 69 ml/min) compared with the less disabled patients (two per patient and 1058, 51 ml/min, p less than 0.05). There was a correlation between the Glasgow Outcome Scale grade and the global cerebral blood flow (r 0.74, p less than 0.05). The perfusion defects may correlate with clinical signs that were not explained by CT or MRI findings. SPECT may complement the clinical evaluation in the assessment of outcome after head injury.

Radiolabelled metaiodobenzylguanidine (MIBG) localizes in adrenergic neurons. A study was carried out to evaluate the uptake of this radiopharmaceutical in cerebral tissues. Twenty-three patients with neural crest tumours, who had no evidence of central nervous system disease, were evaluated. Each patient underwent a diagnostic MIBG study, followed by a therapy dose with 131I-MIBG and subsequent scintigraphy. Focal uptake was seen in the cerebellum (CB), basal nuclei and thalamic region (BNTr), 24 and 48 h postinjection on the diagnostic images. The BNTr to cerebral cortex ratio ranged from 1.05 to 1.79. Uptake was also seen on the days 2, 3, 4 and 6 post-therapy images. Single photon emission computed tomography (SPECT) clearly outlined the uptake in the CB and BNTr. The BNTr to cerebral cortex ratio ranged from 1.10 to 1.85 and CB to cerebral cortex ratio from 1.18 to 2.01. It is hypothesized that the focal uptake observed in the CB and BNTr is due to adrenergic receptor binding. It is felt that SPECT with radiolabelled MIBG may prove to be a useful tracer for mapping the adrenergic receptors in the human brain.

A placebo-controlled study of Ramipril on total and intrarenal flow distribution was carried out in 7 patients with essential hypertension. Cortical nephron flow was measured using radiolabelled tubular secreted radiopharmaceuticals 123I orthoidohippurate or 99mTc mercaptoacetyl triglycine by the transit time distribution technique. Both systolic and diastolic blood pressure were reduced significantly by Ramipril without significant changes in an index of cardiac output or in effective renal plasma flow. Cortical nephron flow increased from 207 +/- 7 to 257 +/- 21 ml/min (mean +/- SEM) p less than 0.05 and the percentage of flow to cortical nephrons increased by 6% (p = 0.05). Ramipril corrects the reduced cortical nephron flow found in essential hypertension.

Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123I and 125I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at various times from immediately to 65 days after injection. Visual displays of the images were processed by standard computer techniques. The model used a human colon-cancer cell line, HT29, and the monoclonal antibody, AUA1, which is specific to an epithelial proliferating antigen. Tumour detection was achieved in all the mice. The smallest tumour detectable appeared to be about 1 mm in diameter. The degree of antibody uptake in a tumour depended on its size and the blood supply of its surrounding tissues We believe that the technology and skills are now available for accurate radioimmunodetection of cancer in man.

Two tumour-associated monoclonal antibodies, HMFG1 and HMFG2, were labelled with iodine-123 and used to detect primary and metastatic ovarian, breast, and gastrointestinal neoplasms by external body scintigraphy in twenty patients with advanced disease. Tumours became visible 3 min to 18 h after injection of labelled antibody. The presence of antibody in the tumours was confirmed by autoradiography and immunoperoxidase staining of surgically removed tissues. The mean tumour uptake of radiolabel was 0.6% of the injected amount. These antibodies can therefore localise specifically to tumours and successful imaging can thus be achieved. This method can complement existing diagnostic techniques and also provide a basis for a selective therapeutic approach to malignant disease.

The distribution of kidney position in the sitting posture has been determined in a series of patients presenting for renography, using radiographic and ultrasonic techniques. Both the craniocaudal distribution of kidney centre positions and the distribution of the differences in depth below the posterior skin surface of the two kidney centres have been found to have a significant standard deviation. The effect of these distributions on the measurement of relative effective renal plasma flow by 131-I Hippuran probe renography has been calculated for the situation in which no kidney localizing techniques are used. The resulting error distribution has an SD of 21.7 per cent in the case of equally divided function.

Using a particular collimated NaI scintillation detector and a kidney phantom containing 131-I, the dependence of the resulting count rates on collimator-kidney geometry has been determined. These results have been used to calculate the geometrical contribution to the error in the measurement of relative effective renal plasma flow (REP) by 131-I-Hippuran renography. When radiographic and ultrasonic methods of localizing the kidneys are employed, this error has been found to follow a normal distribution with a SD of 2.6% in the case of equally divided function. Combination of this error with that from natural movement and statistical fluctuations, as observed using a dose of 10 muCi 131-I-Hippuran, has led to the estimation of a corresponding potential error 11%. Values of the potential error, which is defined as the 99% probability range, have been calculated covering the range of RFP.

Kinetic analysis with probability mapping is an objective method of serial image analysis applicable to radioimmunoscintigraphy. The technique is described and subjected to clinical testing by comparing the prediction of biopsy histology from the probability map in patients coming to operation. In those with ovarian cancer undergoing second-look laparotomy after completing full courses of chemotherapy, the prediction of histology in 108 biopsy sites was 45 true positives and 38 true negatives, sensitivity 80%, specificity 73%, accuracy 77% p less than 0.001. In patients with tumors less than 2 cm diameter, 41 biopsy sites were predicted with a specificity of 78% and an accuracy of 76%, p less than 0.01. The technique is reducing the need for second-look laparotomy in patients with subclinical and subradiological disease. Such disease is suitable for intraperitoneal radioimmunotherapy.

Functional significance of renal artery stenosis (RAS) was assessed by 99Tcm-DTPA radionuclide scintigraphy, using the mean parenchymal transit time (MPTT) of the tracer as an index of renovascular disorder. Two groups of subjects were investigated retrospectively: eight normal live kidney donors; and 11 patients with hypertension, six with and five without significant RAS. MPTT was 171 +/- 11 s in the kidney donors, and there was a significantly prolonged MPTT in patients with RAS, 313 +/- 27 s (p less than 0.05). MPTT was also prolonged in three hypertensive patients with intrinsic renal disorders. The advantages and limitations of this technique are discussed. It is concluded that prolongation of MPTT can detect functionally significant renovascular disorder without pharmacological challenge.

Ocular radioimmunoscintigraphy was performed in 20 patients using 99mTc-labeled monoclonal antibody 225.28S, F(ab')2 fragments. Radioimmunoscintigraphy was positive in 13 patients and the diagnosis of ocular melanoma was confirmed by enucleation of the eye or clinical follow-up. Scintigraphy was positive in one patient with lymph node metastasis from an ocular melanoma. In six patients immunoscintigraphy was negative. Using this technique a sensitivity of 92.8% was achieved for detecting ocular melanomas. Single photon emission tomography helped to separate the lesions situated in the nasal quadrant of the eye from the adjacent nasopharyngeal activity. With appropriate imaging techniques small tumors of the order of 3 x 5 x 3 mm could be detected clearly.

Thirty patients presenting with a pelvic mass were entered into a prospective study on the use of radioimmunoscintigraphy with the 123I-labeled monoclonal antibody HMFG2. The imaging data was obtained without knowledge of the clinical data and compared with subsequent surgical findings. A false-positive diagnosis of ovarian cancer was made in five of ten patients subsequently shown not to have ovarian cancer; thus the technique cannot be used as a screening test. A true-positive diagnosis was made in 19 out of 20 patients shown subsequently to have ovarian cancer. In 18 of these patients the distribution of uptake closely fitted the surgical findings. Methods of improving these results are described. In conclusion, radioimmunoscintigraphy is of no use in determining whether a pelvic mass is due to ovarian cancer, but has benefit in the evaluation of chemotherapy and may, in the future, prevent the need for second-look operations in some circumstances.

The effects of irrigation with sterile and infected saline after acute ureteric dilatation by graded Teflon dilators were evaluated renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F, and 100 ml of sterile or infected saline were then introduced from a height of 60 cm under gravity. One week after irrigation and dilatation the ipsilateral kidney was either functioning less than 10% or there was an obstructive nephropathy. Histology at 3 months suggested that extravasation of infected irrigating fluid was the most likely cause of ureteric stricture formation.

The effects of three methods of acute ureteric dilatation (by graded Teflon dilators, low and high pressure balloon dilators) were evaluated radiologically, renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F. All three methods caused upper urinary tract dilatation and an obstructive nephropathy which had not resolved 96 h after dilatation. Histology at 24 h showed destruction of the transitional epithelium, with inflammation throughout the ureteric wall. Four weeks after dilatation the ureter was still dilated and urothelial nests were seen in the lamina propria and in the muscle coats. There was no evidence of ischaemic necrosis or ureteric stricture formation. The implications of these findings for clinical practice are discussed.

Forty-two patients were evaluated pre- and postextracorporeal shock wave lithotripsy (ESWL) using [99mTc]DTPA renography. A quantitative evaluation showed that the relative renal function decreased 2-3 days post-ESWL on the treated side, and the parenchymal transit time index (PTTI) increased 2-3 days post-ESWL (p less than 0.001) on the treated side and returned to the pretreatment level by 3 wk post-ESWL. The untreated side showed an increase in PTTI 2-3 days post-ESWL (p less than 0.01), which returned to normal by 3 wk post-ESWL. A significantly greater increase in PTTI was seen in patients who received greater than 1,000 shocks as compared with those who received less than 1,000 shocks. Five patients developed obstructing uropathy post-ESWL, when stone fragments caused ureteric obstruction.

A Phase I study in 12 patients with renal disorders compared the simultaneous clearances of 99mTc-labeled mercaptoacetyltriglycine (MAG3) and 131I-labeled orthoiodohippurate (OIH). The ratio of MAG3 to OIH clearance was 0.61 +/- 0.08 as a result of its smaller volume of distribution, ratio 0.65 +/- 0.09, for the clearance half-lives were similar, ratio 1.09 +/- 0.12. A Phase II study performed serially in 20 patients with equal doses of [99mTc]MAG3 and [123I]OIH gave images of equal quality. The relative renal functions were highly correlated (r = 0.97, p less than 0.001) and transit time analyses gave good correlations: parenchymal transit time index r = 0.81, p less than 0.05. We conclude that [99mTc]MAG3 has some advantages over [99mTc]DTPA and is a suitable replacement for [123I]hippuran in routine renal imaging, relative function, and transit time studies, but not for the accurate estimation of the renal plasma flow.

A technique is described for measuring an index of cardiac output, total and individual renal plasma flow, cortical and juxtamedullary nephron flow non-invasively in man with a single injection of 123I-o-iodohippurate. Ibopamine, a dopamine analogue, was administered orally, 200 and 600 mg, in a double-blind, placebo-controlled cross-over study in 6 healthy subjects. No change in pulse, blood pressure, cardiac output, urea, creatinine or electrolytes was seen. Ibopamine reduced effective renal plasma flow and cortical nephron flow and increased urine flow significantly. This may be due to differential vasoconstrictor and vasodilator effects on the two populations of nephrons. Indoramin, and alpha-1 postsynaptic adrenoceptor blocker, was administered orally, 50 mg, in a double-blind, placebo-controlled cross-over study in 14 healthy young males. No change in pulse, cardiac output, urea, creatinine or electrolytes was seen. Indoramin significantly reduced upright but not supine blood pressure and significantly increased effective renal plasma flow. Cortical nephron flow and juxtamedullary nephron flow tended to rise. Plasma renin activity was significantly elevated although there was no change in urinary sodium output. The effect of drugs on intrarenal blood flow distribution may be relevant to the management of essential hypertension.

Since inert gas washout techniques for cerebral blood flow (CBF) measurement are not applicable to asymmetrical pathological states where assumptions about constancy of distribution, volume, and partition coefficients cannot be held to be valid, a new approach to regional and global CBF is described. Regional volume and regional mean transit time are measured independently to give regional volume flow in ml/min. In a pilot study, this noninvasive, quantitative technique has been applied to 37 patients with various clinical responses to subarachnoid hemorrhage. Global CBF and clinical grading were significantly associated. Reduction of regional CBF and spasm of the relevant arterial supply were also significantly associated in these patients.

Nineteen patients with unilateral cerebrovascular disease underwent cerebral blood flow (CBF) measurements; ten had been receiving conventional therapy and then were studied after treatment with captopril without or with a diuretic and nine on conventional therapy were studied twice as a control group. CBF (ml min-1) was measured after an intravenous injection of 99Tcm-labelled patient's red cells with a computer linked gamma camera over the vertex and a probe over the aorta. With deconvolution analysis regional CBF is given by regional cerebral volume divided by regional mean transit time. Results in the captopril group showed on average a 10% fall in mean blood pressure and a 10% rise in blood flow to the affected hemisphere. In the control group there was on average a 4% fall in pressure, together with an 11% fall in CBF to the affected hemisphere. Captopril appears to maintain autoregulation in cerebrovascular disease.

1. A new method, based on the transit time of omicron-iodohippurate sodium (Hippuran) through the kidney, is proposed as an accurate non-invasive means of measuring the intrarenal flow distribution in man. 2. Data from [123I]Hippuran gamma-camera renography are utilized in this method which employs region of interest selection, deconvolution, cross-correlation and curve subtraction to obtain the spectrum of transit times through the cortical and juxtamedullary nephrons. 3. In 12 normal subjects the mean percentage cortical flow was 83.9% (SEM 0.7%) which is approximately the anatomical proportion of cortical nephrons in the human kidney. 4. Cortical flow as a percentage of total was significantly reduced in 21 hypertensive patients, all of whom had no evidence of primary renal disease (mean 74.6%, SEM 1.5%). 5. In both the normotensive and hypertensive groups there was a good correlation between the results obtained from the left and right kidneys of the same patient showing the parallel physiological response of the two kidneys (mean difference 4%, P less than 0.001). 6. Reduction in the distribution of flow to the cortical nephrons in the essential hypertensive patients supports the hypothesis that renal autoregulation is important in this syndrome.

Monoclonal antibodies to epithelial cells, antigenic determinants labelled with I123 and I125, were administered to 10 immunodeficient mice bearing subcutaneous xenografts of human ovarian cancer. Radio scans of the body taken with a gamma camera at various time intervals demonstrated the presence of the cancer in all the mice. The smallest detectable tumor was approximately 1 mm in diameter. In a subsequent clinical study using 123I-labelled monoclonal antibodies in 10 patients with ovarian cancer, tumor detection was achieved in 8 patients, with tumor uptake of labelled antibody ranging between 0.2-2.6%. As a complementary method to existing forms of diagnosis, the targeting of monoclonal antibodies to ovarian cancer cells in vivo raises the hope of achieving early diagnosis in otherwise undetectable ovarian cancer, and provides encouragement to the concept of selective therapy in oncology.

It was considered that the first dose reaction occurring with prazosin may have been due either to hypotension or to a specific reduction in cerebral blood flow. The development of a quantitative non-invasion nuclear medicine technique for cerebral flow has now made it possible to investigate the effects of prazosin on cerebral blood flow in hypertensive patients. This double-blind study showed a significant decrease in BP and a small just significant increase in cerebral blood flow following a single 1-mg dose of prazosin, when compared with a placebo. From these results, it is unlikely that the first dose reactions which occurred with prazosin were due to a specific reduction in cerebral blood flow.

In 20 patients with pelvi-ureteric junction obstruction the results of quantification of the change in renal pelvis size during high-dose intravenous urography with a diuretic, pressure/flow studies, standard renography and deconvolution analysis of the gamma camera renogram have been compared. The results of high-dose intravenous urography and pressure/flow studies correlated well. Renography was unreliable in diagnosing obstruction unless deconvolution analysis of the gamma camera renogram was used to differentiate those showing an obstructive uropathy from those with an obstructing nephropathy.

Sixty-three patients presenting with the clinical problem of renal outflow disorder were studied using 99mTc DTPA. The techniques of frusemide diuresis and parenchymal transit time index analysis were compared and both shown to be successful in aiding the decision as to the presence or absence of significant outflow obstruction.

A monoclonal antibody HMFG2 labeled with iodine 123 (123I) was given to a patient who had ovarian cancer. The scan taken 18 hours after administration of the antibody demonstrated the presence and the position of residual tumor in the pelvis that was not previously detected by ultrasonography and computerized tomography (CT) scanning. The presence of tumor was confirmed by surgery and histologic as well as immunoperoxidase examination of resected tissues. The tumor mass found was less than 0.8 cm in diameter. It is concluded that, in the search for residual or early ovarian cancer in the pelvis, monoclonal antibody scanning using 123I-labeled HMFG2 can complement ultrasonography and CT scanning.

A non-invasive test of nephron function, the renal parenchymal transit time (P.T.T.) index, is shown to be as accurate as antegrade pressure measurements in diagnosis of renal outflow obstruction. It is more sensitive than conventional methods of demonstrating the associated obstructive nephropathy. P.T.T. is useful in following the effects of surgery, or of temporising, in patients with confirmed or potential outflow tract obstruction. Renal radionuclide P.T.T. analysis gives the functional information essential for the management of patients in whom intravenous urography reveals a dilated renal pelvis.