Cyril C. Nimmon

Obstructive nephropathy: successful evaluation with radionuclides.

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.

123I radioiodinated antibody imaging of occult ovarian cancer

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.

Clinical experience with 99mTc-MAG3, mercaptoacetyltriglycine, and a comparison with 99mTc-DTPA

The preparation, application and clinical usage of 99mTc-mercaptoacetyltriglycine, MAG3, a tubular secreted compound, is described in the first 225 patients in a phase III study. Image quality, relative renal function, and renal transit times were compared with a 4 fold greater administered activity of 99mTc-DTPA in 11 patients. Correlation coefficients of 0.94 for relative function, 0.83 for parenchymal transit time index and 0.82 for whole kidney transit time index were found. Frusemide responses were similar. 99mTc-MAG3 is an efficacious radiopharmaceutical for routine renal radionuclide studies, giving excellent image quality in patients with hypertension, poor renal function, obstructive nephropathy or a renal transplant.

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 < 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.

Clinical renography : 25 years on

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.

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 patients 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.

Clinical evaluation of 99mTc diaminocyclohexane, a renal tubular agent with cationic transport : results in healthy human volunteers

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.

Cerebral uptake of MIBG: adrenoceptors visualized?

Radiolabelled metaiodobenzylguanidine (MIBG) localizes in adrenergic neurones. 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.

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.

Total and Intrarenal Flow Distribution in Healthy Subjects: Technique, Acute Effects of Ibopamine and of Indoramin

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.