1. Nuclear Imaging in
Nephro-urology

2. Introduction
 Uses pharmaceuticals – labels with
radionuclides (radiopharmaceuticals) -
radiotracers
 Administers these to patients – radiation
emitted is detected
 Formation of an image using a gamma
camera or positron emission tomography
 Radionuclide imaging / nuclear
scintigraphy
 Shows the physiological function of the
system being investigated

3. Introduction
 Radiotracers – DTPA, MAG3, OIH etc – taken up by
kidneys, then excreted into urinary tract
 Serial frames of posterior view – acquired 20-30 min
immediately after tracer injection
 Frame rate –
 1-3s per frame for one min to assess perfusion
(perfusion phase)
 10-15s per frame for 4 min to assess function
(function phase)
 10-30s per frame to assess urinary system
(excretion phase)

4. Overview of renal
radiopharmaceuticals
Renal handling Radiopharmaceu
tical
Imaging Clinical use
Glomerular
filtration
51 Cr-EDTA No GFR
99mTc-DTPA Yes GFR
Tubular secretion 123I/131I-OIH Yes ERPF
99mTc-MAG3 Yes ERPF
99mTc-EC Yes ERPF
Tubular retention 99mTc-DMSA Yes Cortical imaging
99mTc-GH Yes Cortical imaging

5. Glomerular filtration
 Gold standard – inulin clearance
 Radionuclide of choice – 51Cr-EDTA – clearance
closest to that of inulin
 99mTc-DTPA – technetium-99m-diethylenetriamine
pentaacetic acid – correlates well with 51Cr-EDTA and
inulin
• Taken up by glomerular filtration, not
secreted/reabsorbed by tubules
 99mTc-DTPA can be used for gamma camera imaging
 Least expensive renal radiopharmaceutical
 Low radiation dose
 Small fraction may be bound to protein – not a
problem for routine measurement of GFR
 Once reaches kidney – 20% is accumulated and
remainder flows away, i.e. extraction fraction of DTPA
is 20%

6. Tubular secretion (1)
 p-Aminohippuric acid (PAH) – gold standard
for measurement of tubular cell function and its
clearance – effective renal plasma flow (ERPF)
 123I-OIH and 131I-OIH – cleared by tubular secretion
(small fraction by glomerular filtration)
 Clearance rate – approx 500-600ml/min
 Extraction of 131I-OIH depends on renal plasma flow
and extraction from plasma (proximal tubules)
 123I-OIH – better imaging qualities, more expensive

7. Tubular secretion (2)
 99mTc-MAG3
 highly protein-bound, cleared mainly by
proximal tubules
 High extraction fraction (50%) – better
scintigraphic images
 99mTc-I, I and d,d-ethylenedicysteine
(EC) – better than 99mTc-MAG3

8. 65 year-old with contrast nephropathy on CKD – better image of TC-MAG than DTPA scan

9. Tubular retention
 99mTc-dimercaptosuccinic acid (DMSA)
 Excellent cortical imaging agent
 Concentrates largely in renal cortex (lesser in liver)
 Strongly bound to proteins
 At 2h post-injection : 50% retained in kidneys, no
visualization of urinary collecting system
 99mTc-glucoheptonate (GH)
 Filtered by glomerulus and bound by tubules
 Highly protein-bound – glomerular filtration partial

10. DMSA
 IV injection – bound to proximal tubules
 Indications:
 Assessment of kidneys in acute phase of UTI
(acute pyelonephritis)
 Assessment of kidneys in late phase of UTI –
detection of scar
 Assessment of horseshoe, solitary or ectopic
kidney
 Localisation of poor or very poorly functioning
kidney
 Assessment of renal function in the presence of
an abdominal mass
BNMS guidelines

11. DMSA
 Pitfalls
 Acute and chronic pyelonephritis cannot be distinguished
on the cortical scan. If a defect is present 6 months after
the last UTI then this is a scar
 A recent UTI may cause temporary reduced uptake / focal
defect and a follow-up DMSA scan should be undertaken
 The diagnosis of renal scars is difficult in the infant under
3-6 months of age because of renal immaturity. If
appropriate the scan should be delayed
 Controversies
 To obtain the highest resolution, some centres recommend
the use of a pin hole collimator, however many institutions
obtain high resolution images with clear definition between
cortex and medulla without the use of pin-hole collimation
 Currently there is no evidence to support the routine use of
SPECT in children to delineate focal defects
BNMS guidelines

12. Analytic methods
 Various methods
 Single-sample methods and camera-based
methods suitable for busy clinical practice
 Single-sample – single venous blood sampling
after tracer injection, and plasma radioactivity
is measured
 Plasma activity and injection dose
substituted in a predefined, empiric
equation = renal clearance

13. Analytic methods
 Camera-based methods – renal uptake early
after tracer injection reflects renal function
 Calculate renal function from imaging data without blood
sampling
 A region of interest (ROI) is drawn for each kidney to
estimate activity, then do a background subtraction, then
attenuation correction for depth of each kidney, then
normalized to the injection dose – finally substituted to an
empiric equation = renal clearance
 Less accurate than single-sample method
 Can assess right and left kidney function separately – split
renal function
 Can do combined single-sample and camera-based
methods
Isotopic Scan for Diagnosis of Renal Disease. Yusuke Inoue et al. Saudi Journal of Kidney Diseases and Transplantation. 15(3) 2004; 257-64

14. Analytic methods
 Renogram curves – overview of the time
course of renal radioactivity
 Generated by setting an ROI for each kidney
 Radioactivity in a kidney derives from renal parenchyma,
upper tract and overlapping extrarenal tissues
 Do background subtraction - renal parenchyma and upper
tract
 In normal subjects – a renogram demonstrates rapid
increase during perfusion and function phases, then rapid
decline during excretion phases
 Hypofunction flattens the slopes during the function and
excretion phases
 Obstruction causes delayed excretion
 Cannot discriminate between retention in renal
parenchyma and that in urinary tract – visual assessment
of scintigraphy images needed…

17. Clinical uses:
 Renal clearance measurements
 Obstruction
 Infection
 Renal artery stenosis
 Renal transplant

18. Renal clearance measurements
 GFR and estimation of split renal
function
 Renal Plasma Flow

19. Glomerular Filtration Rate
 Substances suitable for measuring
GFR
 Low protein binding
 Negligible non-renal excretion
 Freely filtered
 Chemically stable and inert
 INULIN – Gold standard

20. GFR
 Radioactive tracers – simplifies sample
measurements
 Single injection
 51Chromium ethylenediamine tetraacetic acid
(51Cr-EDTA) – agent of choice
 99mTc-DTPA – can be used – prepared from
kits - variability in stability and protein-binding
 Short half-life (6 hours)
 Advantage – imaging and GFR measurement
can be performed at the same time

21. GFR - 51Cr-EDTA
 After iv injection – EDTA rapidly diffuses
throughout bloodstream, equilibrates more
slowly with EVF
 Measure the plasma conc at 2, 3 and 4
hours after injection
 Back extrapolation to time of
injectiondistribution volume of extacellular
space, and slope of declining conc is
fractional clearance of this space  GFR
 Expressed in ml/min or normalised to body
surface area

22. GFR - 51Cr-EDTA
 A number of attempts to simplify GFR
measurements
 Considerable variation due to age and body
dimensions
 High errors
 All single injection methods – assume patient
in a steady state with respect to
hemodynamics and fluid exchange
 Not accurate e.g. major surgery, transfusion
or dialysis

23. EDTA
 GFR - plasma clearance curve - which required multiple
blood samples to be taken over a period of several hours
 Slope-intercept method – after numerous simplification
 number of sample : 1 (recommended by the
Radionuclides in Nephrology Committee on Renal
Clearance (Blaufox et al, 1996) )
 It is recommended that the plasma clearance of EDTA
from venous samples be taken as the standard measure
of GFR
 DTPA does have some technical advantages over EDTA
but normal ranges are not so well established
 Small systematic differences have been observed
between GFR measurements obtained from EDTA and
DTPA (Rehling et al, 1984, Fleming et al, 1991, Biggi et
al, 1995)

24. Renal plasma flow
 Tracers that are filtered and actively secreted
by renal tubules – extracted with  efficiency
from plasma perfusing kidneys
 Ortho-idohippurate (OIH) – 90% removed by
kidneys on a single pass  ERPF
 Less widely available
 99mTc-labelled compounds – 99mTc-MAG3:
 Higher protein binding and lower extraction efficiency
 Tubular extraction rate
 Need multiple blood samples for accuracy

25. Clinical uses:
• Renal clearance measurements
• Obstruction
• Infection
• Renal artery stenosis
• Renal transplant

26. Obstructive Uropathy
 Obstruction of the urinary flow
anywhere from the renal pelvis to the
urethra
 Can be acute or chronic
 In adults most commonly caused by
tumor or prostatic enlargement
(hyperplasia or malignancy)
 Need to have bilateral obstruction in
order to have renal insufficiency

27. Prenatal Hydronephrosis
 Prenatal hydronephrosis (collecting
system dilatation) can be identified
on prenatal ultrasound in about 1% of
patients (0.3-4.5% and is bilateral in
37-57% of cases.
 Followup is generally recommended if
the AP diameter of the collecting
system is 7-10 mm during the 3rd
trimester of pregnancy.

28. Prenatal Hydronephrosis
 The first follow up exam should be
performed during the 1st week after
birth- but not during the first 72
hours because of reduced urine
output after delivery.
 On post-natal follow-up, the dilatation
will resolve in 20-50% of cases.

29. Obstruction/Urinary tract
dilatation
 Diuretic renography – diagnostic
work-up of upper tract dilatation, and
follow-up of patients with
hydronephrosis
 Method of choice – to differentiate a
dilated unobstructed urinary system
from a true stenosis
 Can also assess urine flow and renal
function

30. In children:
 Sedation should be avoided – may interfere
with bladder voiding
 Increased radiation exposure to bladder
mucosa – concern
 Receiving the child with parents in a dedicated,
calm environment
 If needed – local guidelines for sedation
 Short inhalation of equimolar mixture of
nitrous oxide and oxygen
J Nucl Med 2006; 47:1819–1836

31. Diuretic renography
 99mTc-mercaptoacetyltriglycine(MAG3) and
123I-orthoiodohippurate (OIH) are preferred
 higher renal extraction ratio and rapid
plasma clearance, especially in infants and
young children and in patients with impaired
renal function
 Use of frusemide 1mg/kg (max 20mg in
children, 40mg adults
 Recommended by Society of Nuclear
Medicine
 European Nuclear Medicine Association

32. Diuretic renography
 Timing of frusemide administration
 20 min or more after tracer injection – max
distension of renal pelvis or ureter can be
visually assessed (F+20)
 15 min before tracer injection – diuretic
response of kidney is maximal (F-20)
 Diuretic response is evaluated by visual and
quantitative interpretation of the dynamic
acquisition
 Postmicturition images are mandatory because
a full bladder may delay urinary flow even in an
unobstructed system

33. Diuretic renography
 The role of bladder catheterization – debated -
not recommended in clinical routine practice
 Older children and adults - renography is
performed after bladder emptying
 Non–toilet-trained children, spontaneous
micturition is usually observed during the
acquisition
 Adequate functioning of the affected
kidney (GFR > 15 mL/min) and adequate
hydration are major determinants of the
response to frusemide

34. Limitation/pitfall of diuretic
renography

35. 6/12 old boy, febrile UTI by age of 2/12, normal ultrasound and VCUG

37. 9 year-old boy – febrile UTI

38. Indirect radionuclide cystography

39. 4 year-old girl treated
conservatively for left PUJ
stenosis detected
prenatally
Left kidney
20min after injection After miction 50 min after injection

41. Clinical uses:
• Renal clearance measurements
• Obstruction
• Infection
• Renal artery stenosis
• Renal transplant

42. UTI
 Frequent in children
 Affect girls 2x > boys
 80% first infections diagnosed during
first 2 years of life
 5% in infants and young children –
fever of unexplained origin
 Diagnosis – urine culture
 Risk of renal damage – delay of
diagnosis/treatment, number of UTIs

43. UTI
 The Subcommittee on Urinary Tract
Infection of the American Academy of
Pediatric Committee on Quality
Improvement recommended imaging
(mainly sonography, VCUG, or
radionuclide cystography) of the urinary
tract in children younger than 2 y old
but considered the role of cortical renal
scintigraphy still to be unclear despite
its recognized high sensitivity

44. Cortical scintigraphy
 Scintigraphy with 99mTc-dimercaptosuccinic
acid (DMSA) – simple and non-invasive
 Static imaging 2-4 hours after iv injection
 Delayed or post-frusemide images in
hydronephrosis
 The sensitivity of 99mTc-DMSA for the
detection of parenchymal defects due to
infection - from 80% to 100%
 does not allow differentiation of acute
pyelonephritis from renal scars

45. Cortical scintigraphy
 Abnormal findings on cortical scintigraphy are found in
52%–78% of children during acute pyelonephritis, and
the risk that a renal scar will develop can reach 60%
 The role of cortical scintigraphy is still largely debated in
acute pyelonephritis but is widely accepted in the
detection of renal scars
 99mTc-DMSA scintigraphy is the reference method
for detecting renal sequelae after UTI, is more
sensitive than sonography, and should be
performed no sooner than 6 mo after the last
documented UTI
 Also used to detect scars in VUR

49. Radionuclide cystography
 Direct radionuclide cystograhy
 A radiologic-VCUG alternative - lower
radiation burden
 As invasive as VCUG – bladder
catheterization
 More sensitive – acquisition is continuous in
both filling and voiding phase
 Indirect radionuclide cystography
 Performed after conventional renography with 99mTc-
MAG3 or 123I-OIH – high excretion rate
 No need catheterization
 Less sensitive and specific than VCUG/direct
cystography

55. Clinical uses:
• Renal clearance measurements
• Obstruction
• Infection
• Renal artery stenosis
• Renal transplant

56. Renovascular hypertension
 3 – 5% of all hypertensive patients
 15 – 30% of referred patients for refractory
hypertension
 Renal hypoperfusion  secondary
activation of renin-angiotension system
 Stenotic or obstructive lesion within renal
artery
 Potential curable cause of hypertension
 70-90% - atherosclerosis
 10-30% - fibromuscular dysplasia

57. Renovascular hypertension
 RVH is a consequence of activation of RAS with
concomitant release of angiotensin II (a
vasoconstrictor) and aldosterone (leading to
plasma volume expansion) to maintain
physiologic renal perfusion by increasing blood
pressure
 Clinical features:
 abdominal bruits, rapid onset of hypertension,
refractory hypertension, unilateral renal atrophy,
azotemia (esp when worsened by ACEi or ARB),
unexplained azotemia/hypokemia
 Episodes of flash pulmonary edema in patients with
relatively well-preserved systolic function
 Gold standard – Renal angiography

59. Captopril-enhanced renography
 To determine which patients can expect normalization of
BP or improvement of BP control after revascularization
 ACEi reduce the conversion of angiotensin I 
angiotensin II - diminishing the vasoconstriction of the
postglomerular efferent arteriole and decreasing the
GFR, which can be detected by scintigraphy
 Both glomerulus-filtered (99mTc-DTPA) and tubule-
secreted (99mTc-MAG3 or 123I-OIH) - currently used
 ACEi – captopril (25-50mg) orally 60min before
renography; or iv enalaprilat (40mg/kg) over
325min >15min before renography

60. Captopril-enhanced renography
 Known pitfalls  erroneous results are
 food ingestion within 4 h before receiving
captopril,
 dehydration, hypotension,
 or a full bladder impairing drainage
 ACEi enhanced renography now is rarely used
as the primary imaging tool
 Most reliable in predicting recovery in patients
with FMD

61. 35 year-old : Doppler ultrasound
showing parvus-tardus pattern with
collapsed resistance index
Normal right kidney

62. Left kidney
Right kidney

64. 75 year-old lady
– OIH study

67. Typical diagnostic workup for
RVH
Doppler sonography, CT
angiography or MRA
ACE inhibitor
renography
Renal
angiography
and treatment

68. Clinical uses:
• Renal clearance measurements
• Obstruction
• Infection
• Renal artery stenosis
• Renal transplant

69. Renal transplantation
 Comprehensive evaluation of renal transplants – in
differential diagnosis of medical and surgical
complications in early post-op and in long-term follow
up
 Selection of patients for biopsy and for various drug
regimens
 Anuric ATN – improving indices of renal function (ERPF,
uptake of tubular tracers) – indicates resolution of tubular
injury
 The protocol: a flow study, scintigram of kidneys, prevoid
and postvoid bladder image, injection site image,
time/acitivity curves of graft and bladder, and quantitative
data of perfusion, function and tracer transit
Report of the Radionuclides in Nehrourology Committee for
evaluationof transplanted kidney (review of techniques).
Dubovsky et al. Semin Nucl Med. 1999 Apr;29(2):175-88

70. Renal transplantation
 Flow study – 99mmercaptoacetyltriglycine or DTPA
 Quantitative analysis and function phase should
include images and time/activity curves
 Serial studies: decline in function and poor
perfusion indicative of acute rejection
 A normally appearing scintigram without cortical
retention, low function – chronic rejection
 Diuretic renogram - to exclude obstruction
Report of the Radionuclides in Nehrourology Committee for
evaluationof transplanted kidney (review of techniques).
Dubovsky et al. Semin Nucl Med. 1999 Apr;29(2):175-88

71. Renal transplantation
 A baseline study should be performed
within 1 – 2 days of operation – to
allow comparison of serial studies
because of deteriorating renal
function
 DTPA – tracer of choice in early
stages
 DTPA/MAG3 can be used later stages

72. Indications for renography in
transplantation

73. Renography in transplantation
 Ultrasound – 1st line evaluation in
renal graft dysfunction
 Renography – must be available on
emergency basis
 Non-visualization – irremediable loss of function
 May not differentiate rejection from ischemia
(RAS)
 ACEi renography – help determine whether
arterial hypertension is dependent on RAS
 Help in diagnosis of urinary complications –
obstruction or leak

74. Graft dysfunction
1d post-
transplantation in
a 41 y-old
woman

77. 5d post-transplantation

78. 6d post-transplantation – sudden anuria and abdominal pain

79. Decreased graft function 5/12
post-transplant, renogram
showed an OIH accumulation
within normal limits, normal peak,
but delayed elimination
1-min images reveal tracer
retention in parenchyma without
outflow impairment – suggesting
potential CNI toxicity

80. Conclusion
 Role of nuclear medicine – in investigation of
renal parenchymal function and upper urinary
tract abnormalities
 Radiation burden low
 Do not require sedation or specific patient
preparation
 Easy to perform
 Knowledge of renal patho-physiology and
recognition of limitation and technical pitfalls
essential