YEAR BOOK 2005
Reprinted from Yearbook Nuclear Medicine 2005, 0-323-02074-7, Pgs. 293-309, M. Donald Blaufox, MD, PhD, with permission from Elsevier
Shikano N, Kanai Y, Kawai K, et al: Transport of 99mTc-MAG3 via Rat Renal Organic Anion Transporter 1. J Nucl Med 2004; 45:80-85
The identification of the mechanism of organic anion transport by the kidney has been a steady although slow development, however, read more about this biological process at https://bestcustompapers.com/ Many of the important transporters in the tubules have now been identified and isolated allowing for in vitro studies of their actions. This is important because of the need to understand renal handling of various therapeutic drugs. This study very nicely clarifies the handling of Technetium-99m-MAG3 by the kidney. Those of you interested in a more detailed discussion may wish to review my commentary which was published in the Journal of Nuclear Medicine1. -M Donald Blaufox, MD PhD
Reference: Blaufox MD: Transport of 99mTc-MAG 3 via Rat Renal Organic Anion, J Nucl Med 2004; 45:86-88.
de Jong M, Valkema R, van Gameren A et al: Inhomogeneous Localization of Radioactivity in the Human Kidney After Injection of (111In-DTPA) Octreotide. J Nucl Med 2004; 45:1168-1171
Methods for calculating dosimetry are extremely complex. In order to derive a model, which is solvable, it is often necessary to make assumptions that are known to be estimations at best. One assumption that almost always is used is that there is homogeneous distribution of activity throughout an organ. This is rarely true and this article shows very clearly how the assumption of homogenous distribution of radioactivity in the kidney, in this case labeled octreotide, is likely to result in a significant error. -M Donald Blaufox, MD PhD
Velasco M, Mateos JJ, Martinez JA et al: Accurate topographical diagnosis of urinary tract infection in male patients with 111indium-labelled leukocyte scintigraphy Eur Jrl of Internal Medicine 2004;(15:157-161)
The role of Nuclear Medicine techniques in the diagnosis of urinary tract and related infections generally has not been appreciated. Although there is increasing utilization of these modalities in pediatrics, in adult medicine very little is done. Patients with prostate disease in particular are easily confused for pyelonephritis or cystitis. It is interesting in this study that among 20 males, the majority with a urinary tract infection associated with fever had prostatic disease. Hopefully, further studies like this will demonstrate the value of Nuclear Medicine techniques in general and white cell imaging in particular in differentiating upper from lower urinary tract infection in adult males who are at risk for acute prostatitis. -M Donald Blaufox, MD PhD
Hitzel A, Liard A, Dacher JN, et al. Quantitative Anlaysis of 99mTc-DMSA During Acute Pyelonephritis for Prediction of Long-term Renal Scarring. J Nucl Med 2004; 45:285-289
Recognition of the important value of 99mTc-DMSA scanning in children with acute pyelonephritis is growing. Although interest in this technique in the United States is rather limited, it is generally accepted throughout Europe by pediatric nephrologists and pediatric nuclear medicine physicians. Along with the ability to determine the presence of acute pyelonephritis in a child with urinary tract infection there is also the potential ancillary data on prognosis. This study presents an approach to that issue which appears to work reasonable well. Since the cut off values for sensitivity and specificity were determined from the population itself, it is necessary for a corroborative prospective study using these values to confirm the results. If confirmed, this would be a very simple and useful way of predicting children at risk for scarring with pyelonephritis. -M Donald Blaufox, MD PhD
Sakran RRW, Chazan B, Colodner R, et al: Long-Term Follow-Up of Women Hospitalized for Acute Pyelonephritis. Clinical Infectious Diseases 2003; 37:1014-1020
Like the study by Imperiale et al1, this investigation revealed a surprisingly high number of people who developed renal scarring after an episode of acute pyelonephritis as determined on 99mTc-DMSA scanning. Since most of our assumptions about the consequences of a single episode of acute pyelonephritis are based on follow up with intravenous urograms, it is possible that the greater sensitivity of the DMSA scan is the basis for the discovery of a larger number of people with permanent scars. Most important is the conclusion that clinically relative renal damage is rare and that this does not lead to renal insufficiency. Although this is true in adults it may not be true in the previously cited study of children. -M Donald Blaufox, MD PhD
Reference Imperiale A, Olianti C, Sestini S, et al: 123I-Hippuran Renal Scintigraphy with Evaluation of Single-Kidney Clearance for Predicting Renal Scarring after Acute Urinary Tract infection: Comparison with 99mTc-DMSA Scanning.
Imperiale A, Olianti C, Sestini S, et al: 123I-Hippuran Renal Scintigraphy with Evaluation of Single-Kidney Clearance for Predicting Renal Scarring After Acute Urinary Tract Infection: Comparison with 99mTc-DMSA Scanning.. J Nucl Med 2003; 44: 1755-1760
This study contains several surprises. Usually initial episodes of acute pyelonephritis are not associated with a significant reduction in renal function. In this series, many of the children had reduced function during an acute infection apparently prior to any renal scarring. The other surprise is the large number of patients in whom renal scars are subsequently noted. Perhaps there is some bias in the types of patients who were referred to this hospital or were referred for DMSA studies. In any event, the study nicely shows that 123I-Hippuran scintigraphy can provide complimentary information to 99mTc-DMSA in evaluating and following up these patients. -M Donald Blaufox, MD PhD
Turkolmez S, Atasever T, Tukolmez K, et al. Comparison of Three Different Diuretic Renal Scintigraphy Protocols in Patients With Dilated Upper Urinary Tracts Clin Nucl Med 2004; 29:154-160
The number of protocols for the evaluation of patients with dilated upper tracts has increased over the last decade. There is now an F + 0 protocol, an F – 15 and an F + 20. The F + 20 of course was the original approach that was modified by Paddy O’Reilly using the F – 15 in patients in whom the renogram was indeterminate.1 It is useful to have a comparison of all three methods as this study has done. The fact that the F + 0 and F – 15 protocols showed no equivocal study while 7 out of 28 patients were equivocal with the F + 20, certainly leans the practitioner in the direction of these alternate approaches. The disadvantage of the injection of Lasix at the time of the injection of the radioactivity, or prior to it, is the lack of a baseline study that in some situations can be very helpful and serves as the justification for the F + 20 study. However, in situations where equivocal tests are to be avoided and where baseline data are not essential this alternate approach is very helpful. It is interesting that it does not appear to very greatly influence the results whether an F + 0 or an F – 15 study is used. -M Donald Blaufox, MD PhD
References: 1. O’Reilly PH, Aurell A, Britton K, et al. Consensus on diuresis renography for investigating the dilated upper urinary tract. J Nucl Med 1996; 37:1872.
Nimmon CC, Samal M, Britton K: Elimination of the Influence of Total Renal Function on Renal Output Efficiency and Normalized Residual Activity J Nucl Med 2004; 45:587-593
The use of deconvolution analysis of the renogram curve has been pioneered by Drs. Britton and Brown from England. A consequence of their work was the development, by Dr. Britton, of the renal output efficiency for the analysis of diuretic renography. The normalized residual activity (NORA) is part of this analysis. The dependence of these parameters on renal function has been debated at various times. This study appears to validate Dr. Britton’s general contention that the level of plasma clearance has minimal effect on the measurement of renal output efficiency. This is appealing since one of the major problems with evaluation of the lasix renogram include the influence of renal function. On the other hand, the authors did find a significant effect of renal clearance on NORA. This is largely a theoretical study and the critical component, which is lacking is a strong clinical demonstration of the value of this methodology in patients with suspected urinary tract obstruction. Most of the studies for support of this parameter come from the same group. It is encouraging that the International Society for Radionuclides in Nephrourology has appointed a committee to evaluate how and when this approach should be used in patients with renal disease. I look forward to seeing the results of that consensus committee and also to some good sized clinical series to validate its use in place of routine visual assessment. -M Donald Blaufox, MD PhD
Khan J, Charron M, Hickeson MP, et al: Supranormal Renal Function in Unilateral Hydronephrotic Kidney Can Be Avoided. Clin Nucl Med 2004; 29: 410-414
There have been a number of reports of supranormal renal function in the presence of unilateral hydronephrosis. This has been ascribed to several potential factors resulting from the effect of obstruction on blood flow in the affected kidney. The authors of this article point out this phenomenon has achieved a somewhat controversial status. Although it is possible that in very acute obstruction there may be an initial vasodilatation of the kidney that results in increased flow, any sustained reaction of this type seems extremely unlikely. It is suggested here that reports of this phenomenon clinically are most likely artifacts resulting from the estimate used to determine individual renal function scintigraphically. The authors suggest that this may be caused by incorrect background subtraction. They report a retrospective study of 57 patients among whom none had supranormal function on the obstructed side. Although this study may not end the controversy in view of the fact that there are animal studies that show early increase in renal blood flow immediately following obstruction for a short period of time, it does serve to emphasize the problems in estimating differential renal function that are associated with the choice of background regions of interest. The assumption that estimation of renal function is more accurate utilizing background subtraction has yet to be proven -M Donald Blaufox, MD PhD
Hunsche A, Press H, Taylor A. Increasing the Dose of Furosemide in Patients With Azotemia and Suspected Obstruction. Clin Nucl Med 2004; 29:149-153
Although I am reluctant to include case reports in my section of the YearBook, this particular one makes a very important point. In patients who have reduced renal function and suspected obstructive urinary tract, the problem in diuretic renography is the question of whether or not there is a diuretic response. The concern in all Lasix renography studies is the issue of a possible failure to respond to diuretics because of reduced renal function. Given a patient with reduced renal function and a failure to respond to Lasix, the question then remains of whether the study should be repeated with a higher dose. This case report shows very nicely that in fact in some patients an increased dose of Lasix is valuable in delivering enough of the diuretic to the kidney to reduce the likelihood of a false positive (obstructive) result -M Donald Blaufox, MD PhD
YEAR BOOK – 2006
Reprinted from Yearbook Nuclear Medicine 2006, 1-4160-3297-5, pgs. 265-273, M. Donald Blaufox, MD, PhD, with permission from Elsevier
Blake GM, Grewal GS: An evaluation of the body surface area correction for 51Cr-EDTA measurements of glomerular filtration rate. Nuclear Medicine Communications 2005; 26:447-451
Many of us in applying body surface area correction to renal function measurements simply look at a table of surface area without spending much time thinking about how that table was derived. Certain measurements become so much a part of clinical medicine that their origins are lost. Although there continues an endless and perhaps at this point unfruitful debate about the best method for measuring glomerular filtration rate, no such debate exists with respect to body surface area correction. It is encouraging given that situation that the authors did not find a very significant difference between the two body surface area methods they tested. However, they should be commended for bringing this potential source of significant error to our attention. -M Donald Blaufox, MD PhD
Fleming JS, Persaud L, Zivanovic MA: Quality control of slope-intercept measurements of glomerular filtration rate using single-sample estimates. Nuclear Medicine Communications 26:737-742, 2005
The problem with any simplified technique is the inherent inverse relationship between accuracy and simplification. Given the problem of an increasing uncertainty of the reliability of the value with increasing simplification, it is worthwhile to consider some quality assurance approach. The authors suggest using the one sample method to control against a slope intercept technique for measuring clearance as a quality control method. At our institution, we routinely calculate the clearance both from the two sample method and from the single sample. In situations where there is an unusually large disparity, the test is either repeated or compared against some other standard. It is nice to see this approach formalized and put in print. Given modern automation, it adds little extra work and provides a nice technique of quality assurance. The discussion about the various possible reasons for error is also worth reviewing for any institution where clearances are performed on a routine basis. -M Donald Blaufox, MD PhD
Fleming JS, Persaud L, Zivanovic MA: A general equation for estimating glomerular filtration rate from a single plasma sample. Nuclear Medicine Communications 26:743-748, 2005
Yet another equation for estimating GFR. What more needs to be said. -M Donald Blaufox, MD PhD
Carlsen, O: The gamma camera as an absolute measurement device: Determination of glomerular filtration rate in 99mTc-DTPA renography using a dual head gamma camera. Nucl Med Commun 2004; 25:1021-1029
The search for a better method for renal clearance seems to be unending. This study reports the incorporation of the gamma camera and some innovative techniques to presumably improve on the accuracy of the measurement. However, a number of important assumptions are made that may not be universal. For instance, the relationship between EDTA clearance and inulin clearance may average out to a 10% difference but in any individual subject this number will vary. I leave it to the reader to decide if this rather complex technique is likely to provide sufficient improvement in accuracy to make it worthwhile, although I have my doubts. What is needed in this age of cost efficacy are some data to show that the values obtained using this technique result in an improvement in patient care or diagnosis over other techniques which are available in general use at this time. -M Donald Blaufox, MD PhD
Yapar AF, Aydin M, Reyhan M, et al: The conditions for which the geometric mean method revealed a more accurate calculation of relative renal function in 99mTC-DMSA scintigraphy. Nuclear Medicine Communications 2005; 26:141-146
This is a very large study of patients in whom relative renal function was calculated both by simple determination of the count rate and also after correction using the geometric mean. As one would expect, there are significant differences between these two methods. The study also makes the point that in younger patients, there is a significant difference as well as in adults and that difference may be exacerbated by unilateral reduction in renal function due to some pathology. These points are useful and interesting but unfortunately due to limitations in the availability of methodology we do not know the answer to the correct value. Although it might seem logical to assume that correction for renal depth using the geometric mean would provide a more accurate measurement of relative renal function, the lack of a gold standard, especially in patients with significant asymmetry of function, leaves this more of a theoretical rather than an absolute proof of the value of the geometric mean. It is not clear why the largest variance occurred in the group of patients who were ten years of age and older. These differences appear to occur in significant numbers even in patients with normal kidneys. -M Donald Blaufox, MD PhD
Mingin GC, Nguyen HT, Baskin LS: Abnormal Dimercapto-Succinic Acid Scans Predict An Increased Risk Of Breakthrough Infection In Children With Vesicoureteral Reflux J Urol 2004; 172:1075-1077
This short article plays an important role in defending the use of the DMSA scan in children with vesicoureteral reflux. The data strongly suggest that the scan has important prognostic value and therefore can play a valuable role in the management of these patients. In making decisions about chronic preventive therapy for infection, it is certainly helpful to choose those patients in whom the likelihood of repeat infection is greater and to be able to spare those patients at low risk from the necessity to take antibiotics for a prolonged period of time. This study suggests that the DMSA scan can play a critical role in making this decision. Even more important is the difficult decision of which children require surgical intervention. Again, the data here suggest that the DMSA scan can be used by the urologist to help decide the urgency for correction of ureteral vesicle reflux. -M Donald Blaufox, MD PhD
Liu Y, Ghesani NV, Skurnick JH, et al: The F+0 Protocol for Diuretic Renography Results in Fewer Interrupted Studies Due to Voiding ^Than the F-15 Protocol. -J Nucl Med 46:1317-1320, 2005
The F-15 protocol for diuretic renography was an innovative and very useful introduction into the concept of evaluation of obstruction. Although obviously numerous modifications are possible, the F+0 protocol is attractive because of the greater simplicity in being able to administer the diuretic and radiopharmaceutical at the same time. The observation that the F+0 protocol is associated with a lower rate of disruption due to voiding is an interesting one and another reason to consider using the F+0 on a more routine basis. A full bladder is a problem not only because of disruption of the study and the need to try to realign the renogram curves and images but also because it is now well accepted that a full bladder can cause an apparent obstruction of the upper tract due to the pressure effect. It is to be expected that the more tolerable the procedure is for the patient and the less movement associated with it, the more accurate the results to be anticipated. -M Donald Blaufox, MD PhD
YEAR BOOK – 2007
Reprinted from Yearbook Nuclear Medicine 2007, 978-0-323-04643-5, pgs. 257-271, M. Donald Blaufox, MD, PhD, with permission from Elsevier
Grenier N, Hauger O, Cimpean A, et al: Update of Renal Imaging Semin Nucl Med 2006; 36:3-15
As diagnostic imaging techniques progressively improved, a number of radiologic approaches to study the kidney have begun to offer significant competition with renal nuclear medicine. Over the next several years as data are accumulated, we will hopefully be able to better understand where radionuclides should be used and where other radiographic techniques are complimentary or have replaced the radionuclide methods. This is a very fine review to put these various methodologies in perspective as they currently exist. -M Donald Blaufox, MD PhD
Szabo Z, Xia J, Mathews WB, et al: Future Direction of Renal Positron Emission Tomography, Semin Nucl Med 2006; 36:36-50
The introduction of new and innovative techniques in renal Nuclear Medicine has declined precipitously during the past several years. However, there is a bright future as more sophisticated techniques become more generally available. The potential role of PET imaging in renal Nuclear Medicine is very promising but is not a simple technique and will require a great deal of investigation to bring it into clinical practice. Some of the more promising applications are reviewed here. -M Donald Blaufox, MD PhD
Blake GM, Gardiner N, Gnanasegaran G, et al: Reference ranges for 51Cr-EDTA measurements of glomerular filtration rate in children. Nucl Med Comm 2005; 26:983-987
One of the advantages of radionuclide techniques in studying renal function in children is the greater ease of establishing reference values. Serum creatinine is a much more complex agent to use in determining normal values because of the interrelationships between age and body size. But even for agents independent of muscle mass, such as the radionuclide clearance techniques, there still remains a difficulty in establishing a normal value. This article is worth reviewing for any center where a significant amount of renal function measurements are made in children. Unfortunately even with studies such as this the problem of defining normality remains considerable as can readily be appreciated by the very wide 95% confidence interval shown in the figure. There is no simple solution to this problem but it remains a practical fact that one of the most valuable uses of clearance techniques is to follow the changes with time and to show normal kidney growth, which is independent of the absolute measurement. -M Donald Blaufox, MD PhD
Aktas A, Haberal M: Classification of Tc-99m DTPA Renograms Based on the Relationship Between Uptake and Perfusion Pattern. Transplantation Proceedings, 2005; 37:4259-4265
The early methods for analyzing renograms were based upon the pattern of the curve itself and some type of visual analysis as shown in the authors’ figure 3. Early on, the major radiopharmaceutical used was 131I hippuran and a great number of studies were devoted to relating the pattern of the renogram before and after transplantation and its evolution from baseline. These early studies were similar to the one presented here. I feel compelled to comment that although the earliest reference noted in this article is 1979, there were many in-depth studies of renogram patterns prior to this. Some of these studies are reviewed by Kountz S1, Blaufox MD2
Reference:
1. Kountz S, Radionuclides and Renal Transplantation. Evaluation of Renal Function and Disease with Radionuclides, Blaufox MD (Ed) S. Karger, Basel, Switzerland, 1972, vol 2, p. 235-248.
2. Blaufox MD, Compartment Analysis of the Radiorenogram and Kinetics of 131I Hippuran. Evaluaton of Renal Function and Disease with Radionuclides, Blaufox MD (Ed), S. Karger, Basel, Switzerland, 1972, vol 2 p 107-124.
Ozcan Z, Anderson PJ, Gordon I: Robustness of estimation of differential renal function in infants and children wity unilateral prenatal diagnosis of a hydronephrotic kidney on dynamic renography: How real is the supranormal kidney? Eur J Nucl Med Mol Imaging 2006; 33:738-744
Anyone who has used radionuclide techniques to measure renal function has surely encountered the phenomenon of supranormal renal function, be it by a simple clearance technique or differential counting. The underlying reason for a supranormal value is very often difficult to find if at all. This study reports that 16.9% of the patients had supranormal function as defined by a greater than 5% difference. However, in our experience, a two standard deviation difference between the two kidneys is about 10%. When one sets the differential renal function at less than 5% as the normal range, then it is expected that the number of patients that will fall outside the normal range will be increased. Our experience is to set it at 10%, which reduces the number of false abnormal values to very few. In fact, the difference noted by the authors support the concept that two standard deviations is 10%. It is not surprising that the differential function varies with age given the many anatomic and physiologic factors involved -M Donald Blaufox, MD PhD
Buyukdereli G, Guney IB: Role of Technetium-99m N, N-Ethylenedicysteine Renal Scintigraphy in the Evaluation of Differential Renal function and Cortical Defects Clin Nucl Med 2006; 31:134-138
Although Technetium-99m N-Ethylenedicysteine appears to be a promising renal radiopharmaceutical as evidenced by this article and many others, it appears that it will never make it to market in the United States. Although there may be advantages of Technetium-99m EC over MAG3 in some situations, and DMSA in others, these do not appear to be enough to warrant application for a new drug here in the United States. It is unfortunate that during the past several years, relatively little progress has been made in the evaluation of renal disease with radiopharmaceuticals. Certainly there is room for more and better agents and potential evaluation of the kidney with PET. Hopefully, this will come to pass. -M Donald Blaufox, MD PhD
Piepsz A, Ham HR: Pediatric Applications of Renal Nuclear Medicine Semin Nucl Med 2006; 36:16-35
If you do radionuclide renal studies in children you must read this article. -M Donald Blaufox, MD PhD
Salem CE, Hoh CK, Wallace AM, et al: A Preclinical Study of Prostate Sentinel Lymph Node Mapping With (99mTC) Diethylenetetramine Pentaacetic Acid-Mannosyl-Dextran Jrl Urology2006; 175(744-748)
The concept of lymphoscintigraphy as a marker for cancer metastases is now very well established in melonoma and breast. These authors seek to extend that concept to prostate cancer. Several other studies have been carried out on prostatic lymphoscintigraphy including one from our group1. Our results in humans were similar to the results noted here in experimental animals. Unfortunately the tracer that we used, which was an excellent lymph node marker was withdrawn from the market. Perhaps this newer agent, (99mTC) Diethylenetetramine Pentaacetic Acid-Mannosyl-Dextran, will also prove equally effective in humans with prostate cancer and will help to guide the urologists in carrying out pelvic lymph node dissection where indicated. -M Donald Blaufox, MD PhD
Reference:
1. Zuckier LS, Finkelstein M, Kreutze, EF, et al: Technetium-99m atimony sulphide colloid lymphoscintigraphy of the prostate by direct transrectal injection. Nucl Med Comm 1990; (11)589-596
Aktas A, Aras M, Colak T: Comparison of Tc-99m DTPA and Tc-99m MAG3 Perfusion Time-Activity Curves in Patients With Renal Allograft Dysfunction. Transplantation Proceedings 2006; 38:449-453
Aktas A, Colak T, Gencoglu A: Indicators of Acute Rejection of Tc-99m DTPA Renal Scintigraphy. Transplantation Proceedings 2006; 38:443-448
Shriki J, Murthy V, Brown J: Renal Oncocytoma on 1-11C acetate Positron Emission Tomography: Case Report and Literature Review Mol Imaging Biol 2006; 8:208-211
It is interesting that a renal oncocytoma can be detected with a 11C acetate positron emission tomography scan. It is surprising that in their review of the various modalities to evaluate a possible renal tumor, the authors omit conventional nuclear medicine methodology. It has been shown that both hippuran and DTPA are taken up by these lesions. Hippuran is the best documented agent and general wisdom suggests that in a tumor such as an oncocytoma, the uptake of hippuran is very strong evidence that it is a benign lesion. 1,2 -M Donald Blaufox, MD PhD
Reference:
1. Lee VW, Allard J, Foster J, et al: Functional oncocytoma of the kidney: Evaluation by dual tracer scintigraphy. J Nucl Med 1987; 28:1911-1914.
2. Choudhri AH, Patel PR, Cunningham, DA: Uptake of 99mTc-DTPA by a renal oncocytoma. Eur J Nucl Med 1987; 13:311-312.