**6. 99Tc-DTPA (Diethylenetriaminepenta-acetic acid)**

#### **6.1 Physiological and analytical data**

Like 51Cr-EDTA, 99Tc-DTPA is an isotopic marker with a low molecular weight (393 Da)(Durand et al., 2006). DTPA may be labeled with another isotopic marker (113mIndium (Johansson & Falch, 1978; Reba et al., 1968; Piepsz et al., 1974), 169Ytterbium (Perrone et al., 1990; Russell et al., 1985)) but technetium 99 is the most used up to now. The 99Tc-DTPA is also used in Nuclear Imagery (isotopic nephrogram) for instance to measure separately the function or the right and left kidney (Biggi et al., 1995; Hilson et al., 1976; Kainer et al., 1979). However, we will only discuss GFR measurement based on plasma and/or urinary methods with 99Tc-DTPA. GFR can also be estimated with external counting using gamma camera (namely the "Gates" method) (Gates, 1984; Russell, 1987) but this method is not precise enough to be considered as a reference method for measuring GFR. For some authors, the GFR estimation given by the Gates method is even less performing than the creatinine clearance (Owen et al., 1982; Goates et al., 1990; van de Wiele C. et al., 1999; Ma et al., 2007; Mulligan et al., 1990; Galli et al., 1994; Ginjaume et al., 1985; Rodby et al., 1992; Tepe et al., 1987; Aydin et al., 2008; De Santo et al., 1999; Fawdry et al., 1985; Durand et al., 2006).

Doses of injected 99Tc-DTPA are totally safe (10 MBq)(Kempi & Persson, 1975; Durand et al., 2006). If the GFR measurement is coupled with nephrogram, the radioactive dose is however 40 to 200x higher than a simple GFR measurement with 51Cr-EDTA (Kempi & Persson, 1975; Griffiths et al., 1988). The half-life of 99Tc-DTPA is short (6.05 h) which imposes that the GFR measurement is realized quickly after the samplings, which is a practical inconvenient compared to 51Cr-EDTA (Owen et al., 1982). The 99Tc-DTPA measurement is as precise as other isotopic methods. The most relevant critic regarding 99Tc-DTPA is its potential binding to protein. This aspect has been debated in the literature. Some authors described a binding to plasma proteins from 2 to 13%, which implies an underestimation of GFR, especially when GFR is measured by plasmatic clearance (Kempi & Persson, 1975; Agha & Persson, 1977; Klopper et al., 1972; Biggi et al., 1995; Houlihan et al., 1999; Rehling et al., 2001). These high percentages could however been explained by the lack of purity of the first available preparations of 99Tc-DTPA (Rootwelt et al., 1980; Rehling et al., 2001; Fleming et al., 2004; Carlsen et al., 1980; Russell et al., 1983; Kempi & Persson, 1975). This hypothesis has been well illustrated in 1980 by Carlsen who studied and compared 51Cr-EDTA clearances with 4 different commercial preparations of 99Tc-DTPA. This author showed different results according to the preparation used (Carlsen et al., 1980). The binding to protein may also be studied by different methodologies (ultrafiltration, electrophoresis, precipitation, *in vitro* or *in vivo,* in humans or in animals etc)(Rehling et al.,

How Measuring Glomerular Filtration Rate? Comparison of Reference Methods 31

**GFR methods Statistics Results** 

Wilcoxon

urine : p<0.05 plasma : p<0.05

0.97

0.97 =0.93x+6.8

0,969 1,02±0,14

0.77 =0.94x+33.7

> 0.96 =x+4.4 0.93

0.85 =0.84x+8.4 0±18

Ratio urinary

plasma 99Tc-DTPA and urinary clearance of inulin Correlation Regression

Correlation Ratio

Correlation Regression

Correlation Regression r²

Correlation Regression BAr

urinary and plasma clearance with bolus 99Tc-DTPA: Urinary and plasma clearance: samples at 5, 10, 20, 40, 60, 90, 120, 150, 180, 210, 240, 270, 300 min

urinary clearance and constant infused rate 99Tc-DTPA urinary clearance

urinary clearance and constant infused rate 99Tc-DTPA plasma clearance: samples at: 60 and 150 min

urinary clearance and constant infused rate 99Tc-DTPA: urinary clearance with bolus

urinary and plasma clearance with bolus 99Tc-DTPA: urinary clearance with bolus

7 to 182 Inulin:

10 to 117 Inulin:

**(mL/min/ 1.73 m²)**

20 Nephrectomy 11 to 76 Inulin:

45 NP ±10 to 140 Inulin:

NA Lupus 23 to 123 Inulin:

**References Sample Population GFR range**

37 Healthy and CKD

29 10 heart

grafted 11 renal grafted 10 donors

(Rehling et al., 1984)

(Shemesh et al., 1985)

(Notghi et al., 1986)

(Petri et al., 1988)

(Lewis et al., 1989)

2001; Russell et al., 1983; Jeghers et al., 1990). For example, Rehling found a binding to protein of 10-13% but this author was also the only one who found a significant and comparable binding to protein for 51Cr-EDTA and iothalamate (Rehling et al., 2001). The subject is finally still debated (Jeghers et al., 1990). Another potential critic about 99Tc-DTPA is the very poor available data on its physiological handling. A study in a dog model argued for the absence of tubular secretion and reabsorption (Klopper et al., 1972).
