In vivo detection of deposition of radiolabeled lupus antikidney antibody and its inhibition by soluble antigen.

UNLABELLED: This investigation in an animal model was designed to test the feasibility of using radiolabeled lupus antikidney antibody to show renal deposition in vivo and the ability to block this deposition with a binding peptide. METHODS: BALB/c mice received injections of radiolabeled murine anti-DNA antibody, antibody with no DNA binding capability, and DNA antibody simultaneously with blocking peptide. RESULTS: Significantly higher renal deposition of anti-DNA antibody than of antibody without DNA binding capability occurred in the animals at 48 h after injection (5.21% of the injected dose per gram of tissue versus 2.5%, P < 0.0004) and at 7-8 d after injection (1.44% versus 0.20%, P < 0.00004). The simultaneous injection of blocking peptide with anti-DNA binding antibody significantly reduced the renal deposition of the anti-DNA antibody at 48 h (1.53%, P < 0.00001) and at 7-8 d (0.64%, P < 0.0017). CONCLUSION: This study showed the feasibility of using a radiolabeled antibody to evaluate deposition of anti-DNA antibody in the kidney and the successful use of a peptide to block antibody deposition-a strategy that may be useful for renal preservation in lupus. These data support the possibility of using antikidney-labeled antibodies to evaluate immunologic renal disease in vivo in humans.

Parenchymal mean transit time analysis of 99mTc-DTPA captopril renography.

UNLABELLED: Proposed renal hemodynamic mechanisms of captopril suggest that quantitation of renographic retention parameters should help identify patients suspected of having renovascular disease. The parenchymal mean transit time (MTT) is theoretically superior to other measures of retention, but data supporting its superiority are few. METHODS: Two groups of subjects were studied with diethylenetriamine pentaacetic acid (DTPA) baseline and captopril renography, one (n = 43) with demographically defined essential hypertension (group I) and the other (n = 60) with a high prevalence of renovascular disease (group II). Abnormal parenchymal MTT values were derived from the statistical confidence limits of group I data and then applied to group II subjects for comparison with angiographic results. RESULTS: Depending on the sensitivity of the threshold chosen, specificity varied, but the overall accuracy of baseline parenchymal MTT for renovascular hypertension detection ranged from 54% to 58%. Change in parenchymal MTT (post-captopril - pre-captopril) accuracy was 55%-61% and was not significantly different. Neither method improved on previously reported quantitative or qualitative criteria. Group II subjects had significantly worse renal function than did group I subjects, and 23% had nondiagnostic renograms. CONCLUSION: Parenchymal MTT analysis of DTPA captopril renography is not more accurate and offers no advantages compared with qualitative renography or with more commonly used renographic measures in our subjects. This may relate to the high prevalence of renal dysfunction in our population. In subjects with renal dysfunction, the low sensitivity and the trend toward low specificity of parenchymal MTT do not support its routine use for the evaluation of renovascular disease among patients suspected of having renovascular hypertension.

PET imaging in oncology.

The role of positron emission tomography (PET) during the past decade has evolved rapidly from a pure research tool to a methodology of enormous clinical potential. Perhaps the most striking development is the use of PET in oncology. PET imaging is approved in the United States for lung, lymphoma, colon, and melanoma cancer imaging. Data are accumulating rapidly to attest the efficacy of Fluorine-18 fluorodeoxyglucose (FDG) imaging in a wide variety of malignant tumors with sensitivities and specificities often in the high 90s. FDG uptake has been shown in tumors of the head and neck, ovary, breast, musculoskeletal system, and neuroendocrine system as well. The major role of PET has emerged as a reliable method for evaluating and staging recurrent disease. But it also has an important role in differentiating benign and malignant primary tumors. This has been shown particularly well in the differential diagnosis of solitary lung nodules. Although FDG has emerged as the dominant radiopharmaceutical for PET imaging in oncology, numerous other compounds are being evaluated. It is likely that more specific and efficacious compounds will be introduced during the next decade. F-18, because of its highly favorable physical characteristics, is likely to become the technetium of PET imaging. The next decade will witness an explosive growth of PET technology in oncologic imaging.

Optimization of urinary FDG excretion during PET imaging.

UNLABELLED: Accumulation of fluorodeoxyglucose (FDG) activity in the urine interferes with the visualization of pelvic and, sometimes, abdominal abnormalities. Although this is a major problem, there are few data on the physiological variables affecting FDG urinary excretion that are critical to minimizing urinary FDG interference during PET imaging. METHODS: The excretion of FDG in urine was determined during 90 min in four groups of rats (n = 24) under the following conditions: normal, hydrated, hydrochlorothiazide treated and phlorizin treated. FDG clearance rates were measured in both normal and phlorizin-treated animals and compared with the glomeruler filtration rate measured with 99mTc-diethylenetriamine pentaacetic acid. We measured FDG excretion in 10 patients who had no known renal disease and were undergoing PET scanning (divided into two groups: hydrated and dehydrated) to relate the animal data to humans. RESULTS: The hydrated and phlorizin-treated animals had the highest excretion of FDG (39.68+/-5.00 % injected dose (%ID) and 45.64+/-9.77 %ID, respectively). Animals given the hydrochlorothiazide had the highest urinary volume, but the percentage excreted was comparable with the normal rats. Measurement of the clearance of FDG in animals before and after the administration of phlorizin determined the amount of FDG reabsorbed in the proximal tubules to be 56%+/-9.15%. The hydrated patients had a higher excretion of FDG than dehydrated patients (16.98+/-1.99 %ID versus 14.27+/-1.00 %ID, P < 0.021), and the volume of urine voided was significantly higher (P < 0.020). CONCLUSION: Hydrochlorothiazide increases urine volume without enhancing FDG excretion. The hydration of patients before PET scanning may lead to more FDG reaching the bladder. Reduction of bladder activity by more frequent voiding facilitated by increased urine volume in hydrated patients may be offset by increased delivery of FDG to the bladder. A preferable means of increasing urinary volume without increasing delivery of FDG to the bladder may be the use of a diuretic.

Consensus on renal cortical scintigraphy in children with urinary tract infection. Scientific Committee of Radionuclides in Nephrourology.

A questionnaire related to cortical scintigraphy in children with urinary tract infection was submitted to 30 experts. A wide consensus was reached on several issues related to planar images: 99mTc dimercapto succinic acid (DMSA) appears as the most appropriate tracer for renal imaging; dynamic tracers are considered to be inferior, in particular 99mTc diethylenetriaminepentaacetate, which is not recommended. The general opinion is that DMSA scintigraphy is not feasible with a minimal dose below 15 MBq, whereas the maximum dose should not be higher than 110 MBq. The dose schedule generally is based on body surface area, and sedation is only exceptionally given to children. Images are obtained 2 to 3 hours after injection, preferably with high resolution collimators; pinhole images are used by only half of the experts. Posterior and posterior oblique views are used by most of the experts, and the posterior view is acquired in supine positions. At least 200.000 kcounts or 5 minute acquisition is required for nonzoomed images. As a quality control, experts check the presence of blurred or double outlines on the DMSA images. Color images are not used and experts report on film or directly on the computer screen. As far as normal DMSA images are concerned, most experts agree on several normal variants. Hydronephrosis is not a contraindication for DMSA scintigraphy but constitutes a pitfall. Differential renal function generally is measured, but no consensus is reached whether or not background should be subtracted. Most of the experts consider 45% as the lowest normal value. A consensus is reached on some scintigraphic aspects that are likely to improve and on some others that probably represent persistent sequelae. There is a wide consensus for the systematic use of DMSA scintigraphy for detection of renal sequelae, whereas only 58% of the experts are systematically performing this examination during the acute phase of infection.

Prospective study of simultaneous orthoiodohippurate and diethylenetriaminepentaacetic acid captopril renography. The Einstein/Cornell Collaborative Hypertension Group.

UNLABELLED: Captopril renography (CR) has been established in the past 10 yr as a useful diagnostic test for renovascular hypertension. However, direct comparison of tubular and glomerular tracers, quantitative criteria, comparison of quantitative and qualitative results and the reliability of the results in renal failure have not been described in a systematic, prospective fashion. METHODS: Same-day baseline and CR using 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) and [131I]orthoiodohippurate (OIH) were simultaneously performed in two groups of hypertensive subjects, one with demographically defined essential hypertension (n = 43) and the other (n = 60) with a high prevalence of renovascular disease, defined with angiograms. Quantitative criteria for abnormal CR were derived from results among the subjects with essential hypertension. Qualitative analysis was performed using widely established criteria. RESULTS: There were no statistically significant differences between quantitative and qualitative accuracy, between OIH and DTPA or among quantitative parameters. The best accuracies for quantitative CR were 56% with DTPA (n = 57) and 60% with OIH (n = 60), in both cases using the relative renal uptake parameter. Qualitative CR (n = 60) had accuracies of 43% (DTPA) and 50% (OIH), both hindered by 29 (DTPA) and 25 (OIH) abnormal but nondiagnostic studies. Two false-positive studies were detected. Twenty-seven of 29 nondiagnostic studies were associated with a glomerular filtration rate of <50 ml/min (n = 17), one small kidney (n = 17) and/or bilateral renal artery stenosis (n = 16). Supplemental measurement of in vitro stimulated plasma renin activity insignificantly (p > 0.10) and improved accuracies to 63% (DTPA) and 70% (OIH), without introducing additional false-positive tests. CONCLUSION: Orthoiodohippurate and DTPA have comparable accuracy in prospective simultaneous evaluation of CR. False-positive studies are fewer than 5%. The accuracies of quantitative and qualitative criteria do not differ significantly but may be improved by supplemental use of the in vitro stimulated plasma renin activity. In individuals with renal insufficiency, small kidneys and/or bilateral renal artery disease, up to 48% of CR studies are abnormal but nondiagnostic.

Single-sample methods to measure GFR with technetium-99m-DTPA.

UNLABELLED: Many single-sample methods have been suggested to simplify the methodology of glomerular filtration rate (GFR) measurement. The relative accuracy of these competing methods is still not clear for clinical practice. METHODS: Fifty-four GFR studies with 99mTc-DTPA were performed on 37 adult patients (serum creatinine 0.8-10 mg/dl). Each study included a UV/P, plasma clearance method (three-sample) and single-sample methods. The single-sample methods used were those of Christensen and Groth (modified by Watson), Constable, Dakubu, Groth and Aasted, Jacobsson, Morgan, Russell and Tauxe. RESULTS: When the GFR > or = 30 ml/min (n = 26), all of the single-sample methods were highly correlated with UV/P. The correlation of the single-sample method with the plasma clearance was higher than with UV/P. In this group (GFR > or = 30 ml/min), the Groth 4-hr sample method had the best value of both absolute difference and percent absolute difference (mean +/- s.e. = 11.05 +/- 2.51 ml/min and 14.08% +/- 2.43%, respectively). Most single-sample methods do not perform well at GFR < 30 ml/min (n = 28), and none of them has a good correlation with UV/P or plasma clearance at this level of renal function. However, the Groth and Aasted's 4-hr sample method was the best compared with others (mean +/- s.e. = 8.43 +/- 1.30 ml/min for absolute difference, and 65.91% +/- 16.70% for percent absolute difference). CONCLUSION: Single-sample methods may not correctly predict GFR in advanced renal failure. Groth and Aasted's method with 4-hr plasma sample has both the lowest mean absolute difference and percent absolute difference in both the group with GFR > or = 30 ml/min and GFR < 30 ml/min. All methods perform acceptably at GFR > or = 30 ml/min.

Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. SHEP Cooperative Research Group.

CONTEXT: Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. OBJECTIVE: To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. DESIGN: Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). INTERVENTION: Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. MAIN OUTCOME MEASURES: Fatal and nonfatal heart failure. RESULTS: During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. CONCLUSION: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

Report of the Radionuclides in Nephrourology Committee on renal clearance.

The need for simple and accurate methods to measure renal function is self-evident. This need increases as techniques for intervention become available. The demand for evaluation of individual kidney function has increased with its role in the diagnosis and follow-up of unilateral renal disease and in decision making for conservative or surgical treatment based on residual renal function. The role of nuclear medicine in this area has been inhibited by confusion about conflicting methodologies. This report is meant to provide guidance to those centers that would like to initiate clearance procedures but have difficulty in choosing appropriate methodology.

Becquerel and the discovery of radioactivity: early concepts.

It has been 100 years since Becquerel discovered radioactivity shortly after he learned of Roentgens discovery of x-rays at a meeting of the French Academy of Science. His discovery in 1896 was a direct consequence of his work and that of his father and grandfather on phosphorescence and fluorescence. It resulted from the serendipitous use of uranium salts, which have known phosphorescent properties, to reproduce Roentgen rays with the mistaken notion that they were a related phenomenon. Intense investigation by Becquerel and others rapidly revealed the differences in these radiations and led to the discovery of beta, alpha, and gamma rays and the properties of radioactivity in numerous other substances. The work of Becquerel was acknowledged by Madame Curie to be the primary influence on the direction of her thesis toward the work that led to the isolation of radium and the introduction by her of the term radioactivity to describe these phenomena. Although the unit of radioactivity is now called the Becquerel in acknowledgement of his accomplishments, few people, even in the nuclear medicine field, are fully aware of the breadth and importance of his work. This article hopefully will help to resolve this.

Exercise renography in untreated subjects with essential hypertension.

UNLABELLED: Exercise induced renal dysfunction is reported to occur in treated hypertensive patients but not seen normotensive subjects. It is unclear if this phenomenon is related to the disease or to treatment. METHODS: Four normal volunteers and 15 hypertensive subjects (antihypertensive medications were discontinued for more than 4 wk) were studied with upright radionuclide renography at rest and during bicycle exercise. The amount of exercise was sufficient to increase the heart rate at least 20 bpm above the resting value. All subjects were healthy, without evidence of left ventricular hypertrophy renal disease or hypertensive retinal disease. BUN, serum creatinine concentration and urinalysis were normal in all subjects. Renograms were performed for 12-15 min after injection of either 1 mCi[123]orthoidohippurate (OIH) or 2-7 mCi 99mTc-mercaptoacetyltriglycine (MAG3). Visual analysis and mean transit time calculation were performed on the rest and exercise studies. RESULTS: Seven of 14 hypertensive subjects and none of the normal volunteers demonstrated abnormal prolongation in renal transit during exercise which was not seen on the resting renogram. Four of these seven subjects had a history of hypertension for 2 yr or less. CONCLUSION: About 50% of individuals with mild-to-moderate hypertension and normal renal function may have abnormal renal transit of renal excretion agents during exercise, although their baseline studies are normal. This finding is unassociated with therapy and appears to be related directly to the pathophysiology of essential hypertension.

Cost efficacy of the diagnosis and therapy of renovascular hypertension.

UNLABELLED: Numerous competing diagnostic modalities and the lack of data about therapeutic benefit result in controversy concerning the identification and treatment of renovascular hypertension. METHODS: Meta-analyses were used to examine the cost efficacy of renovascular hypertension diagnosis and treatment. Sensitivity, specificity and predictive value were calculated for captopril renography, Doppler, the captopril test and arteriography. Sensitivities and specificities were used to project cost per patient cured or improved for each modality. This was compared with the lifetime cost of medical therapy. Cost efficacy was calculated using a hypothetical population (1000 patients, a prevalency rate of 30% for renal artery stenosis, expected cure or improvement rate of 0.77 after angioplasty). RESULTS: The sensitivity, specificity and positive predictive values were similar for all modalities except the captopril test, which had a significantly lower sensitivity. The specificity was similar for all procedures; Doppler was highest but was mitigated by a 17% technical failure rate. The cost per patient cured or improved is greatest for arteriography and lowest for the captopril test. The relationship between cost per patient cured and the number of patients diagnosed in the population was calculated (relative value = (1/cost) x number patients detected). The relative value of captopril renography and arteriography is similar. Doppler and the captopril test have the lowest relative value. If angioplasty reduces medication by three drugs, the savings is $5807 to $8046 per patient. Surgical therapy is not cost-effective. CONCLUSION: Screening for renovascular hypertension is not cost-effective at a prevalence less than 30%, but captopril renography is equally cost-effective as arteriography and obviates the need for an arteriogram in many patients.