A prospective study of 123I-labeled monoclonal antibody imaging in ovarian cancer.

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.

Validation of renal output efficiency as an objective quantitative parameter in the evaluation of upper urinary tract obstruction.

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.

Ocular radioimmunoscintigraphy: sensitivity and practical considerations.

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.

Radionuclide evaluation pre- and postextracorporeal shock wave lithotripsy for renal calculi.

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.

Technetium-99m MAG3, a comparison with iodine-123 and iodine-131 orthoiodohippurate, in patients with renal disorders.

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.

Kinetic analysis and probability mapping applied to the detection of ovarian cancer by radioimmunoscintigraphy.

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.

Imaging prostate cancer with technetium-99m-7E11-C5.3 (CYT-351).

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.

Global and regional cerebral blood flow. Noninvasive quantitation in patients with subarachnoid hemorrhage.

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.

The influence of geometrical factors in 131-I-hippuran renography.

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.

Kidney position and the measurement of relative uptake of 131-I Hippuran in renography.

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.

Cerebral blood flow in hypertensive patients with cerebrovascular disease: technique for measurement and effect of captopril.

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.

Comparison of a corticopelvic transfer index with renal transit times.

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.

A prospective study comparing SPET with MRI and CT as prognostic indicators following severe closed head injury.

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.

Cerebral uptake of MIBG: adrenoceptors visualized?

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 radiopharmaceutical for imaging areas of lymphocytic infiltration: 123I-interleukin-2. Labelling procedure and animal studies.

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.

Predictive value of captopril transit renography in essential hypertension and diabetic nephropathy.

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.

Validity of the mean parenchymal transit time as a screening test for the detection of functional renal artery stenosis in hypertensive patients.

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.