Nuclear Medicine Resources Manual

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CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

250

Adults are given 4 MBq

Cr-EDTA, 10 MBq

99m

Tc-DTPA or 4 MBq

125

I-

iothalamate. Children receive 0.074 MBq/kg body weight (maximum 4 MBq)

Cr-EDTA, 5–7 MBq

99m

Tc-DTPA or 2–3 MBq

125

I-iothalamate. The minimum

volume of injection is 1.0 mL.

5.4.8.4. Equipment

The equipment required for glomerular filtration rate studies is:

—A Venflon hypodermic needle;

—A three way stopcock;

—A 100 mL volumetric flask;

—A 50 mL volumetric flask;

—Glass counting vials;

—A 1 mL tuberculin (TB) syringe;

—A 1.000 mL precision pipette;

—Water;

—A centrifuge;

—A dose calibrator;

—Counting vials;

—A gamma ray vial counter (well type).

5.4.8.5. Patient preparation

Patients should be in a well hydrated condition. It is desirable for children

to come to the laboratory with an intravenous route already established.

5.4.8.6. Procedure

(a) Strategy for drawing blood sample(s)

The number of blood samples and the timing for drawing of the

samples should be based on an estimation of the expected clearance (GFR)

value.

A preliminary estimation of GFR can be made by entering the weight,

age, sex and serum creatinine into a Kampmann nomogram (Appendix 2). For

reasons of feasibility, the blood sample needed for the determination of serum

creatinine can be taken together with the blood sample that is taken for

determination of background activity immediately before injection of the

radiopharmaceutical.

5.4. NEPHROLOGY AND UROLOGY

251

Patients with an expected GFR of more than 30 mL/(min · 1.73 m

)

should be examined through a single sample method. The plasma sample

should be drawn 4–5 hours after injection in adults and after 90–120 min in

children.

Patients with an expected GFR of less than 30 mL/(min · 1.73 m

) should,

as the first choice, be studied with a procedure that includes urine collection.

Urine sampling should always be included in the procedure for patients with

oedema and ascites.

Alternatively, for patients with renal failure, their GFR can be calculated

from a single plasma sample taken after 24 hours (

Cr-EDTA only), or with a

multisample method.

When the estimated GFR is 15–20 mL/(min · 1.73 m

), blood samples

should be taken between 3 and 5 hours post-injection. When the estimated

GFR is less than 15 mL/(min

· 1.73 m

), blood samples should be obtained 5

and 24 hours post-injection.

Formulas for calculation according to the single sample and multisample

methods are presented in Appendix 1 to this section.

(b) Urine collection

When a urine collection technique is utilized, urine should be collected at

2–3 and 3–4 hours with blood samples at 150 and 210 min. Correction for the

time delay due to the transport of urine from the kidneys to the bladder in the

well hydrated patient can be made as follows:

Time delay (min) = 3.6 + 2.6 × [amount over time (mL/min) of diuresis]

–1

When a urine collection is made, the amount of residual urine in the

bladder should be estimated.

Plasma concentrations should be corrected to the concentration expected

in an individual with a body surface area of 1.73 m

. This can be done by the

equations from Ham (see Bibliography to this section).

Procedural issues concerning preparation of standards, injection of

radiopharmaceutical, drawing of blood samples and centrifugation are

described in Appendix 2 to this section.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

252

5.4.8.7. Interpretation

Interpretation should be made with reference to a set of normal values

(Fig. 5.1).

Children aged 2 years and above should have a kidney function

corresponding to that of a 20 year old, provided the result is normalized to a

body surface area of 1.73 m

. For children younger than 2 years, special

reference values should be used.

The 95% confidence interval for the day-to-day variation of a single GFR

measurement in adults is ±14%.

GFR (mL/(min·1.73m²))

Age (years)

FIG. 5.1. Normal values of GFR (SD stands for standard deviation and NV for normal

value).

5.4. NEPHROLOGY AND UROLOGY

253

Appendix 1 to Section 5.4.8

FORMULAS FOR CALCULATION OF GFR

(a) Multisample method in adults and children

The plasma time–activity curve usually fits a two exponential model. It is,

however, only necessary to determine the slow exponential component, since

the contribution of the fast component to the total area under the curve is small

and can be corrected for.

The first step of the multisample method is to calculate a preliminary

clearance, Cl

, as

= Q

/(A/b)

where Q

is the injected amount of radioactivity, b is the slope of the slow

component, as determined from one blood sample drawn at the beginning and

another drawn at the end of the recommended time interval for drawing of the

blood samples, and A is the intercept of the extrapolated slow component with

the y axis.

In adults the final clearance, Cl

, can then be obtained by insertion of Cl

into:

= 0.99Cl

– 0.0012Cl

In children, the formula to be recommended is

= 0.87Cl

(b) Single sample methods in adults

(1) Clearance of

99m

Tc-DTPA in adults is calculated using the following

formula:

ln ( )

() ( 1)

corr

tgt n

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

254

where

V = 8116.6A – 28.2

g(t)

corr

(n – 1) = (1.70 × 10

–6

t – 1.20 × 10

–3

)Cl

n–1

– 7.75 × 10

–4

t + 1.31

C(t) = background subtracted plasma activity in the sample

taken t minutes after the injection

= injected activity

V =

99m

Tc-DTPA distribution volume (mL)

A = body surface area (m

)

Start by calculating g(t) = 9.55exp(–0.0336t) + 1.18exp(–0.000461t) to

yield an initial value Cl¢. Use this initial value to calculate an initial g(t)

corr

value. Insert this value in the formula above and iterate until Cl¢

– Cl¢

n–1

< 0.1.

This formula is applicable for any t > 180 and < 300 min.

(2) Clearance of

Cr-EDTA in adults is calculated using the following

formula:

Cl¢

where

V = 10800A – 5578.6

g(t)

corr

(n – 1) = (–4.18 × 10

–6

t + 6.43 × 10

–4

)Cl

n–1

+ 1.60 × 10

–6

× t

– 0.00103t + 1.25

C(t) = background subtracted plasma activity in the sample

taken t minutes after the injection

= injected activity

V =

Cr-EDTA distribution volume (mL)

A = body surface area (m

)

Start by calculating g(t) = 0.324exp(–0.0121t) + 1.13exp(–0.000289t) to

yield an initial Cl

¢ value. Use this to calculate an initial g(t)

corr

value. Insert

this value in the formula above and iterate until Cl

– Cl¢

n–1

< 0.1 mL/min.

This formula is applicable for any t >

180 and < 300 min.

()

() ( )

corr

tg t n

5.4. NEPHROLOGY AND UROLOGY

255

(3) Clearances of

Cr-EDTA of less than 21 mL/min in adults are

calculated using the following formula:

C¢

where

C(t) = background subtracted plasma activity in the sample taken

1440

min after the injection

A = body surface area (m

)

= injected activity

(1) Clearance of

Cr-EDTA in children is calculated using the following

formula:

where

V = 5867A

1.1792

g(t) = 1.01exp(–0.000110t) + 0.538exp(–0.0178t)

C(t) = background subtracted plasma activity in the sample taken t

minutes after the injection

= injected activity

V =

Cr-EDTA distribution volume (mL)

A = body surface area (m

)

This formula is applicable for any t > 90 and < 120 min for children

between 1 and 15 years of age.

(2) Clearance of

Cr-EDTA in infants is calculated using the following

formula:

9.2ln ( )

+ 87.2

ln ( ) 1.73

()

¥Ct

tg t A

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

256

C¢

where

V = 6980A

1.23

g(t) = 1.01exp(–0.00008t) + 0.42exp(–0.017t)

C(t) = plasma activity in the sample taken t minutes after the

injection

= injected activity

V =

Cr-EDTA distribution volume (mL)

A = body surface area (m

)

The formula above is applicable for any t > 90 and < 120 min for infants

less than 1 year of age.

Appendix 2 to Section 5.4.8

PROCEDURE FOR PREPARATION OF SOLUTIONS AND

HANDLING OF BLOOD SAMPLES

(a) Preparation of stock solution:

(1) Fill the 50 mL volumetric flask half full with water. Mark it properly,

identifying it as the stock solution. Add date.

(2) Withdraw an aliquot from the radiopharmaceutical solution using

the 1.0 mL TB syringe. Do not exceed 55 MBq (1.5

mCi) or well

counter dead time count losses may occur.

(3) Add water to bring the syringe volume to 1.0 mL.

(4) Record the activity in the syringe by means of a dose calibrator.

(5) Transfer the syringe contents into the volumetric flask; flush at least

once. Then fill the volumetric flask with water to the 50 mL level.

Shake gently.

(6) Record the emptied syringe in the dose calibrator to determine

residual activity.

(7) Calculate the activity per millilitre of the stock solution. Note date

and time in a protocol.

ln ( )

()

¥¥

tgt A

5.4. NEPHROLOGY AND UROLOGY

257

(b) Preparation of standards:

(1) Fill the 100 mL volumetric flask half full with water. Mark it

carefully as the standard solution.

(2) Carefully pipette 1.0 mL of the stock solution into the 100 mL

volumetric flask.

(3) Fill the flask to 100 mL with water. Shake the flask gently.

(4) Carefully pipette 1.0 mL of the thus produced standard solution into

a glass counting vial. Use a clean pipette. Label as ‘Standard 1’. Add

date.

(5) Using separate pipettes prepare by a similar procedure two

additional standards (Standards 2 and 3).

(6) Set the standards aside for later counting with plasma samples.

(7) The three standards should be recounted for each clearance

measurement performed on that same day. A substantial variation in

counts between standards indicates a pipetting error and new

standards should be prepared.

(1) Start an intravenous injection and attach a three way stopcock to the

intravenous line.

(2) Attach a 10 mL saline syringe to one of the ports containing approx-

imately 10 cm

of 0.9% saline for injection.

(3) Attach the dose to the last port of the three way stopcock.

(4) Inject the dose through the three way stopcock.

(5) Flush the dose injection syringe twice by drawing saline into the dose

syringe and inject into the patient. Inject the remainder of the saline

through the three way stopcock.

(6) Remove the assay syringe, stopcock and intravenous tubing for

calculation of residual activity.

(d) Procedure for blood sampling:

(1) Insert an intravenous line for drawing blood samples.

(2) Attach a three way stopcock to the intravenous line.

(3) Attach a 10 mL syringe containing heparinized saline to the second

port.

(4) Attach a syringe for the blood sample.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

258

(5) Approximately 30 s before the time the blood sample is needed, start

to withdraw blood back into the heparinized saline syringe to clear

the line of heparin.

(6) After approximately 15 s, turn the stopcock so that about 5 mL of

blood can be withdrawn into the blood sample collection syringe.

(7) Withdraw blood and note the midpoint of the blood collection

period as the time when the sample was collected.

(8) Turn the three way stopcock back so that the heparinized saline can

be injected back into the patient. Inject approximately 5 mL of

heparinized saline to clear out the stopcock and the tubing.

(9) Inject the withdrawn blood into a tube containing acid citrate

dextrose (ACD) or a minute volume of heparin to prevent clotting.

(10) Clean out the three way stopcock with sterile cotton swabs to

remove any residual blood and radioactivity.

(11) Replace as necessary the heparinized syringe with a new syringe

containing heparinized saline.

(12) Repeat the procedure for all subsequent blood samples.

(13) Inject the anticoagulated blood into a centrifuge tube and spin it to

separate the red cells from the plasma.

(14) Carefully pipette 1.0 mL of plasma into the counting vial. Do not

disturb the interface between the plasma and the red cells.

(e) Procedure for centrifugation:

(1) Ensure that the centrifuge is balanced.

(2) Centrifuge for 15 min at a speed to exceed 2000g.

(3) When the centrifuge stops, remove the clear, colourless ultrafiltrate

and pipette immediately. Pipette 1.0 mL from each assembly into

test tubes. Cap each tube and count immediately.

(4) Record the counts and the time each sample was counted.

BIBLIOGRAPHY TO SECTION 5.4.8

BLAUFOX, M.D., et al., Report of the Radionuclides in Nephrourology Committee on

renal clearance, J. Nucl. Med. 37 (1996) 1883–1890.

BROCHNER-MORTENSEN, J., Routine methods and their reliability for assessment

of glomerular filtration rate in adults, Dan. Med. Bull. 25 (1978) 181–202.

— Current status on assessment and measurement of glomerular filtration rate, Clin.

Physiol. 5 (1985) 1–17.

5.4. NEPHROLOGY AND UROLOGY

259

BROCHNER-MORTENSEN, J., HAMMERICH, B., CHRISTOFFERSEN, J.,

Assessment of renal function from plasma urea and plasma creatinine in children,

Scand. J. Urol. Nephrol. 16 (1982) 229–326.

CHANTLER, C., BARRATT, T.M., Estimation of glomerular filtration rate from

plasma clearance of

Cr edetic acid, Arch. Dis. Childhood 47 (1972) 613–617.

CHRISTENSEN, A.B., GROTH, S., Determination of

99m

Tc-DTPA clearance by a

single plasma method, Clin. Physiol. 6 (1986) 579–588.

FJELDBORG, P., BROCHNER-MORTENSEN, J., Determination of

Cr-EDTA

clearance in infants by a single capillary blood sample, Scand. J. Clin. Lab. Invest. 46

(1986) 335–340.

FLEMING, J.S., et al., Comparison of radionuclide estimation of glomerular filtration

rate using technetium-99m diethylenetriamine-penta-acetic acid and chromium-51

ethylenediamine-tetra-acetic acid, Eur. J. Nucl. Med. 18 (1991) 391–395.

GRANERUS, G., AURELL, M., Reference values for

Cr-EDTA clearance as a

measure of glomerular filtration rate, Scand. J. Clin. Lab. Invest. 41 (1981) 611–616.

GROTH, S., Calculation of

Cr-EDTA clearance in children from the activity in one

plasma sample for transformation of the biexponential plasma time–activity curve into a

monoexponential with identical area below the time–activity curve, Clin. Physiol. 4

(1984) 61–74.

HAM, H.R., PIEPSZ, A., Estimation of glomerular filtration rate in infants and in

children using a single-plasma sample method, J. Nucl. Med. 49 (1991) 555–559.

HILSON, A.J.W., MISTRY, R.D., MAISEY, M.N., Technetium-99m-DTPA for the

measurement of glomerular filtration rate, Br. J. Radiol. 49 (1976) 794–796.

KAMPER, A.L., NIELSEN, S.L., Chromium-51-EDTA plasma clearance in severe

renal failure determined by one plasma sample, Scand. J. Clin. Lab. Invest. 49 (1989)

555–559.

MÅRTENSSON, J., GROTH, S., REHLING, M., GREF, M., Chromium-51-EDTA

clearance in adults with a single-plasma sample, J. Nucl. Med. 39 (1998) 2131–2137.

REHLING, M., et al., Simultaneous measurement of renal clearance and plasma

clearance of technetium-99m-labelled diethylenetriamine-penta-acetate,

Cr-labelled

ethylenediamine-tetra-acetate and inulin in man, Clin. Sci. 66 (1984) 613–619.

RUSSELL, C.D., BISCHOFF, P.G., ROWELL, K.L., Quality control of technetium-

99m DTPA for measurement of glomerular filtration: Concise communication, J. Nucl.

Med. 24 (1983) 722–727.