ORIGINAL ARTICLE 
Annals of Nuclear Medicine Vol. 13, No. 6, 383-387, 1999 

Validity of 99mTc-DMSA renal uptake by planar posterior-view method in children 

Eriko TSUKAMOTO,* Kazuo ITOH,** Chietsugu KATOH,* Takafumi MOCHIZUKI,* Toru SHIGA,* Koichi MORITA* and Nagara TAMAKI* 

*Department of Nuclear Medicine, Hokkaido University School of Medicine **Department of Radiology, JR General Hospital 

Renal uptake of 99mTc-DMSA has been quantified by various methods. The aim of this study is to obtain a normal value for 99mTC-DMSA renal uptake calculated by the posterior view method and age variation, and to assess its clinical validity. Scintigrams of 238 children (0-12 years) with 99mTc-DMSA were reviewed. All the children had a clinical history of primary vesicoureteral refiux and/or neurogenic bladder, ureteral or urethral anomalies. Their kidneys were divided into two groups, "normal" and "abnormal" according to their scintigraphic findings and split renal functions. Percent renal uptake per injected dose (% RU) was quantitated from planar images at 2 hours after injection of an age-adjusted dose (26-95 MBq) of 99mTc-DMSA. Calculated total % RU, individual % RU of the right and left kidneys (mean+-sd) in patients with normal kidneys were 40.7+-5.0%, 20.2+-3.0%, 20.4+-2.7%, respectively. There was no significant correlation between % RU and age (r = 0.231). Longitudinal variation in the % RU in 9 patients ranged from 1.2% to 18%. Our conventional method for quantifyng % RU is simple, practical and feasible in routine clinical practice, especially for children under follow up. 

Key words: 99mTc-DMSA, % renal uptake, normal value, age-dependency 

INTRODUCTION 

THE QUANTIFICATION of renal uptake with radionuclide studies is a simple and non-invasive way to assess the renal function. Renal uptake of 99mTc-DMSA is considered to express functioning renal mass.1-3 It depends on blood flow to the kidneys, glomerular filtration and tubular transport mechanisms. The term "functioning renal mass" does not express a single function but a more complex physiology and radiopharmaceutical behavior. It closely relates to other measurements of renal function, especially effective renal plasma flow,4-6 but the precise mechanisms of uptake is unknown7 and how it corresponds to clinical situations in each patient remains unclear. Nevertheless % renal uptake (% RU) of 99mTc-DMSA may be used as an index of renal function and to 

 Received April 12, 1999, revision accepted August 9, 1999.
 For reprint contact: Eriko Tsukamoto, M.D., Department of Nuclear Medicine, Hokkaido University School of Medicine, Kita- 15, Nishi-7. Sapporo 066-8638. JAPAN.
 E-mail: ertsuka@ med.hokudai.ac.jp 

see the change in renal function at follow up. A simple method for calculating % RU is desirable in routine practice, especially in children under follow up. Several methods for quantifying the renal uptake of 99mTc-DMSA in children have been proposed: by using only the posterior view of planar imaging,8 anterior and posterior view planar imaging,9,10 and SPECT.11 We previously reported the method for calculating % RU of 99mTc-DMSA from posterior planar data at 2 hours after injection.12 It is a simple and practical way to calculate % RU and needs shorter examination time than other methods.
 The aim of this study is to obtain normal values by means of our method and its age variation. We also discuss the clinical validity of our method. 

PATIENTS AND METHODS 

Patients 
We reviewed scintigrams with 99mTC-DMSA in 238 children with VUR and/or ureteral or urethral abnormalities. The age ranged from 0 to 13 years (average 6.2 years). There were 103 girls and 135 boys. 

Imaging 
Patients who could not cooperate in the 99mTc-DMSA study were sedated prior to the study. 99mTc-DMSA was prepared by adding freshly eluted 99mTc to a commercially available freeze-dried kit (Daiichi Radioisotope Lab. Co., Tokyo). A single rotating gamma camera (Toshiba GCA602) equipped with a low energy high-resolution parallel-hole collimator was positioned posteriorly with the patient in the supine position. Posterior planar images were taken precisely 2 hours after injection of an age-adjusted dose (26-95 MBq) of 99mTc-DMSA for a preset time of 5 minutes on a 512 x 512 matrix. Supplemental posterior oblique images were also obtained. After the completion of the planar study, SPECT projection images were acquired on a 128 x 128 matrix for 20 seconds at each of the 60 positions over 360 degree rotation. They were reconstructed by means of 5 point pre-smoothing and using a Shepp and Logan digital filter. Conventional coronal images in relation to somatome axis and reoriented coronal images in relation to the visceral axis of the kidney after correction for renal axis rotation were generated.
 % RU of 99mTc-DMSA was calculated from planar posterior image data using the equations previously described12 (see appendix). For quantitation, physical decay of 99mTc from the time of injection to the planar study and tissue attenuation of gamma rays from 99mTc-DMSA in the kidney were corrected mathematically. The linear attenuation coefficient of 99mTc was set at -O.153. The renal depth (cm) was estimated from the equation for body weight (kg) and height (cm) previously reported by Itoh and Arakawal3: depth of the right kidney = 17.3 x (weight/height)-0.8099, depth of the left kidney = 14.8 x (weight/height)-0.6997 . 

Selection of Scintigrams 
The most recent scintigrams were used for the analysis when the examination was performed on more than one occasion in one patient. Serial %RU from repeated examinations were compared by calculating the coefficients of variation.
 Two experienced nuclear physicians reviewed the scintigrams (both planar and SPECT images) and classified the kidneys as "normal" and "abnormal" by consensus. The kidneys were classified as "normal" when they had smooth outlines, no focal loss of cortex, no contractions on both planar and SPECT images and when their split renal functions were in the 45-55% range. Their serum creatinine and blood urea nitrogen were within normal limits. 

Statistical Analysis 
% RU of 99mTc-DMSA and patients' age were compared by linear regression. 

RESULTS 

Of 238 children reviewed, 68 patients had bilaterally normal kidneys. Total % RU of 99mTc-DMSA in these 68 patients ranged from 29.0% to 51.7% (mean+-SD: 40.7+-5.0). Right % RU and left % RU ranged from 13.5% to 28.0% (mean+-SD: 20.2 +-3.0) and 14.1% to 26.1% (mean+-SD: 20.4+-2.7).
 There was no significant correlation between age and total % RU of 99mTc-DMSA and age (r = 0.231 , N.S.) (Fig.1) in the patients with normal kidneys.
 Serial % RUs of bilaterally normal kidneys were obtained in 9 patients examined on more than two occasions (3-6 occasions). Their scintigrams were interpreted as normal throughout the series of examinations. The coefficients of variation of the serial % RU ranged from 1.2 to 18.4% (Fig. 2). 

DISCUSSION 

In order to calculate the renal uptake of 99mTc-DMSA in children, various non-invasive methods and their normal values have been reported.8-11 They are around 50% as shown in Table 1.8-11 Our results are a little less than previously reported but they seem to correspond them. There are several factors which have a significant influence on quantifying renal uptake14 such as renal depth correction,15-18 acquisition timing,19,20 size of regions of interest21,22 and background correction.7,18 We quantified % RU from posterior image data alone 2 hours after injection. It needs a shorter examination time than other methods. Murase et al.17 investigated % RU of 99mTc-DMSA calculated by three different methods: the posterior method including the method with renal depth correction which we used, the conjugative-view method (by means of the anterior and posterior imaging) and the SPECT method. He said that our method overestimated renal uptake more than other methods. Nevertheless, our present results were smaller than those calculated with other methods. This may be due to other factors such as acquisition timing. He showed that calculated data correlated significantly with those estimated by other methods. % RU of normal kidneys in our study did not show a wide range compared to those previously reported. Morris et al.9 reported normal renal values calculated by the conjugative-view method showing a wider range than ours. One of the reasons for this wide range may be the different attenuation caused by different organs, intestines in front of and muscles behind the kidneys, although the same attenuation coefficient was used for the correction. As to acquisition time as an another factor influencing the quantification of % RU, most previous reports proposed 6 hours after injection as reasonable timing8,11,23  because renal uptake of 99mTc-DMSA increases for 6-8 hours and then reaches a plateau.1,10,11 In our hospital, we have performed both imaging and estimating % RU 2 hours after injection. The main reason for this timing is to shorten the patient waiting time to avoid additional sedation of patients. Our smaller estimated % RU may be due to this early timing compared to other methods. We previously investigated the time course of uptake of 99mTc-DMSA in 12 patients (including adult patients).5 Net counts in the region of interest over the kidneys increased as a function of time and reached a plateau 2 hours after injection, whereas % RU, corrected with physical decay and renal depth, increased for up to 4 hours. Flower et al.19 compared renal uptake of 99Tcm-DMSA 2 hours and 4 hours after injection with that at 6 hours. Measured renal uptake (mean+-sd) at 2 hours was 0.79+-0.06 of that at 6 hours. Standard deviation was reasonably small, although it was smaller at 4 hours (mean+-sd: 0.94+-0.04). Calculation of the renal uptake of 99mTc-DMSA at 2 hours after injection is reasonable for routine clinical use, shortening the patient's waiting time and avoiding additional sedation, which have great benefits in actual practice in children.
 Age-independency of % RU was shown in the present study. Morris et al.9 and Evans et al.10 reported similar results, whereas Groshar found slight reversed correlation between age and % RU.11 This difference may be caused by the difference in the methods for calculation. Age-independency makes it possible to use % renal uptake at follow up of renal function in children, especially in children with VUR who need long term follow up.
 The coefficient of variation in multiple measurement of % RU in 9 patients ranged from 1.2 to 18.4%. In a patient whose coefficient of variation was 18.4%, the first renal uptake was measured at the age of 2 months. First % renal uptake was measured as 27.3% whereas the renal uptake measured at between 1 and 4 years-old ranged from 42% to 45.3%. It is reported that the maturation of the kidney tubules is almost completed at 6 months of age 24 Therefore, there is a possibility of incompletion of maturation of the kidney tubules at the age of 2 month. The difference of region of interest size drawn by different operators might have caused great value of coefficient of variation, 12.0%, in another patient. In the remaining 7 patients, coefficients of variation were under 7.5%. They were reasonably small for evaluation of renal uptake at follow up.
 In conclusion, our conventional method for quantifying % renal uptake is simple, practical and feasible for routine clinical use, especially in children during follow up . 

APPENDIX 

Total and individual percent renal uptake (total % RU, right % RU and left % RU) is calculated by means of the following formula:
 Total % RU = right % RU + left % RU
 Right % RU = Rnet/e-0.153 Dr/(D0 x Tpast)
 Left % RU = Lnet/e-0.153 D1(D0 x Tpast)
 Rnet = Rroi - Rbg, Lnet = Lroi - Lbg
  Rroi,Lroi:count in the region of interest right(Rroi) or left(Lroi) kidney
  Rbg,Lbg:count in background of the right(Rbg) or left(Lbg) kidney
  0.153:the linear attenuation coefficient of 99mTc
  Dr,D1: distance from skin to right(Dr) or left(D1) kidney
 D0 = (Cpre - Cpost)
  Cpre: Preinjection syringe count
  Cpost: Postinjection syringe count
 Tpast = (1/2)-(Texam/6.04)
  Tpast:Physical decay of 99mTc from the time of injection to data acquisition
  Texam: time between injection and data acquisition
  6.04: physical half life of 99mTc 

REFERENCES 

1. Godley ML, Ransley PG, Gordon I, Risdon RA, Vivian G, Todd-Pokropek A. The relationship between renal parenchymal mass and absolute quantitation of 99Tcm-DMSA uptake. An experimental study in the growth pig. Nacl Med Commun 6: 377-388, 1985. 

2. Taylor A Jr. Radiopharmaceuticals for the measurement of 'functioning renal mass. ' In: Blaufox MD, ed., Basle, Karger, pp. 60-83, 1989. 

3. Muller-Suur R. Radiophannaceuticals: their intrarenal handling and localization. In: Murray IPC, Ell PJ, eds., Nuclear Medicine in Clinical Diagnosis and Treatment. London, Churchill Livingstone, pp. 195-212, 1994. 

4. Kawamura J, Hosokawa S, Yoshida O, Fujita T, Ishi Y, Torizuka K. Validity of 99mTc dimercaptosuccinic acid renal uptake for an assessment of individual kidney function. J Urol 119: 305-309, 1978. 

5. Taylor A Jr. Delayed scanning with DMSA: a simple index of relative renal plasma flow. Radiology 136: 449-453, 1980. 

6. Motizuki T, Itoh K, Tsukamoto E, Kanegae K, Katoh C, Nakada K, et al. Assessment of renal scarring and parenchimal function by Tc-99m MAG3 and Tc-99m DMSA. J Nucl Med 37 (suppl): 290P, 1996. (abstract) 

7. Piepsz A, Dobbeleir A, Ham HR. Effect of background correction on separate technetium-99m-DTPA renal clearance. J Nucl Med 31 : 430-435, 1990. 

8. Gordon J, Evans K, Peters AM, Kelly J, Morales BN, Goldrich N, et al. The quantitation of 99Tcm-DMSA in pediatrics. Nucl Med Commun 8: 661-670, 1987. 

9. Morris SC, Chittenden SJ, Rivens I, Heary TA, Vastone C, Meller ST. Absolute 99Tcm-DMSA renal uptake in children: a study of 321 kidneys. Nucl Med Commun 16: 566-571, 1995. 

10. Evans K, Lythgoe MF, Anderson PJ, Smith T, Gordon I. Biokinetic behavior of technetium-99m-DMSA in children. JNucl Med 37: 1331-1335, 1996. 

11 . Groshar D, Moskovitz, Gorenbcrg M, Frankel A, Jerusalmi J, Livine PM, et al. Quantitative SPECT of technetium-99m-DMSA uptake in the kidneys of normal children and in kidneys with vesicoureteral refiux: detection of unilateral kidney disease. J Nucl Med 35: 445-449, 1994. 

12. Itoh K, Asano Y, Kato C, Tsukamoto E, Nakada K, Nagao K, et al. Quantitation of absolute and relative renal uptake using 99mTc-DMSA: sequential change in time and correlation to 99mTc-DTPA uptake. KAKU IGAKU (Jpn J Nucl Med) 27: 237-242, 1990. 

13. Itoh K, Arakawa M. Re-estimation of renal function with 99mTc-DTPA by the GATE's method. KAKU IGAKU (Jpn J Nucl Med) 24: 389-396, 1987. 

14. Oei HY. Dynamic and static renal imaging. In: Murray IPC, Elli PJ, eds., Nuclear Medicine in Clinical Diagnosis and Treatment. London, Churchill Livingstone, pp. 213-227, 1994. 

15. Maneval DC, Magill HL, Cypess AM, Rodman JH. Measurement of skin-to-kidney distance in children: implications for quantitative renography. J Nucl Med 31 : 287-291 , 1990. 

16. Conrad GR, Wesolowski CA. Avoidance of errors related to renal depth during radionuclide evaluation of renal perfusion. Clin Nucl Med 12: 956-957, 1988. 

17. Murase K, Tanada S, Ishine M, Yokoyama M, Hamamoto K. Methods for measuring the renal uptake rate of 99mTc-dimercaptosuccinic acid (DMSA): a comparative study. Eur J Nucl Med 16: 725-731, 1990. 

18. Granerus G, Moonen M. Effects of extra-renal background subtraction and kidney depth correction in measurements of GFR by gamma-camera renography. Nucl Med Commun 12: 519-527, 1991. 

19. Hower MA, Meller ST, Chittenden SJ, Fielding SL, Evans K, Gordon I. Absolute 99Tcm-DMSA renal uptake in children. Nucl Med Commun 16: 572-574, 1995. 

20. Taylor A Jr, Lallone RL, Hagan PL. Optimal handling of dimercaptosuccinic acid for quantitative renal scanning. J Nucl Med 21 : 1190-1993, 1980. 

21. Fine EJ, Axlrod M, Gorkin J, Saleemi K, Blaufox MD. Measurement of effective renal flow: a comparison of methods. J Nucl Med 28: 1393-1400, 1987. 

22. Itoh K, Kato C, Shiga T, Tamaki N. Interobserver variance in quantitation of the renal uptake of Tc-99m-MAG3 by a gamma camera method. J Nucl Med 37 (suppl): 293P, 1996. (abstract) 

23. Groshar D, Frankel A, Iosilevsky G, Israel O, Moskovitz B, Lovin DR, et al. Quantitation of renal uptake of technetium-99m DMSA using SPECT. J Nucl Med 30: 246-250, 1989. 

24. Lythgoe MF, Gordon I, Anderson PJ. Effect of renal maturation on the clearance of technetium-99m-mercaptoacetyl triglycine. Eur J Nucl Med 21: 1333-1337, 1994.