Urological applications of Radionuclides

Historical Aspects
 Nuclear medicine involves the injection of a
radiopharmaceutical (radioactive drug) into a patient for either
the diagnosis or treatment of disease. The history of nuclear
medicine began with the discovery of radioactivity from uranium
by the French physicist Antoine-Henri Becquerel in 1896,
followed shortly thereafter by the discovery of radium and
polonium by the renowned French chemists Marie and Pierre
Curie.
 During the 1920s and 1930s radioactive phosphorus was administered to
animals, and for the first time it was determined that a metabolic process
could be studied in a living animal. The presence of phosphorus in the
bones had been proven using radioactive material. Soon 32 P was
employed for the first time to treat a patient with leukemia. Using
radioactive iodine, thyroid physiology was studied in the late 1930s.
Strontium-89, another compound that localizes in the bones and is
currently used to treat pain in patients whose cancer has spread to their
bones, was first evaluated in 1939.
 A nuclide consists of any configuration of protons and
neutrons. There are approximately 1,500 nuclides, most of
which are unstable and spontaneously release energy or
subatomic particles in an attempt to reach a more stable state.
This nuclear instability is the basis for the process of
radioactive decay , and unstable nuclides are termed
radionuclides
 NUCLEAR REACTORS
 CYCLOTRONS
 GENERATORS
 Used for producing radionuclides
Radio tracer

A Biological tracer may be defined as a

very small quantity of a substance that can
be used to explore the function of an organ
or system without disturbing the normal
physiologic and metabolic processes
Renal radio pharmacy

 99mTc most commonly used

 6hrs half life
 140 KeV gamma energy
 Compounded with DTPA DMSA ,GH MAG.
 Phosphates n phosphanates
 51Cr has a half of 27.8 days
 radioactive decay is low so used for blood
sampling and for imaging
 I131,I123 used for renal tubular function
studies
 I131 has half life of 8 days
 I123 has half 13.2 hrs
 Iodinated hippurate is actively secreted by
renal tubules
 70%of the compound is excreted in the urine
in 30 mins
Ga citrate

 In tracer doses after IV binds to transferrin

 Half life 78hrs
 Within 24hrs excreted by the kidneys after
that by colon
 Xenon is more soluble in fat than in blood
 If the patient is caused to rebreathe from a closed
system containing radioactive xenon mixed with air
or oxygen the patient becomes more and more
radioactive with fat accumulating the major part of
the activity
 If the patient is then caused to breathe air alone the
washout of the xenon from the tissue can be
observed with nuclear medical instruments
 The rate of washout correlates with the blood flow 2
the organ of area
 90m tc gh is injected intravenously
 The material is found in the plasma and the blood clearance is rapid
 The gh clears by both tubular secretion and glomerular filtration
 70% of the urine of the normal subject
 6%of the dose is retained in each kidney largely in the cortex permitting
imaging of the cortex 3 to4 hours after injection
 A normal variation in each is clearance by the liver into the gallbladders
and intestines
 99m tc dmsa is slowely injected iv
 It is distributed in the plasma loosely bound to plasma proteins
 The plasma with a half time of 60 mins and concentrates in the renal cortex
 16% of the activity is excreted within 2 hrs
 At 2hrs 15%is concentred in each kidney this increases to 20% by 6hrs
 Imaging is best performed 3hrs or more after injection
 99m tc mag3 also know as mertiatide
renal tubular agent

 The plasma protein binding of mag3 is

approximately as great as that of o1h

 Mag3 has a plasma clearance of

approximately half that of o1h as a result

of decreased glomerular filtration and

lower tubular secretion
Dosimetry

 Ionising radiation exposure risk present for

both nuclear studies n other radio graphic
procedures.
 but in the latter it is accurately determined

if the unit is calibrated

 in theformer it depends on the biological
handling physical properties patient
dosage.
 Dose measured by number of atoms
disintegrating /sec
 Measured by millicurie 3.7x10 7 disinteg/sec
 Micro curie is 3.7x104 disinteg /sec
 SI unit is megaBECQUERAL SO 1Mci is 37M
Bq
 A RADIONUCLIDE WITH A LONG HALF
LIFE WILL CAUSE MORE RADIATION TO
THE PT
 Bladder has the highest exposure can b
reduced by voiding
 Thyroid exposure reduced by Lugols iodine
Instrumentation

 GAS detectors
 GEIGER MUELLER
 survey meter
 DOSE calibrator
 Solid crystal detector
 The imaging device commonly used is Anger
camera
 It has a single crystal made of NaI doped
with thallium 50cm in diameter .25-.375
inchess thick under matrix of PM tubes
numbering 37-91
 Front of the crystal protected by a lead
collimater with holes
Renal imaging

 The arrival of activity recorded in the form of

renal vascular studies.
 All technetium products can be used for
vascular studies.
 Vascular seq at 1 frame per 2 sec faster seq
decide for children.
 Higher imaging rates may deteriorate the
image
l

 Static images collected immediately after the

vascular seq upto several hours as many as
1million counts may be seen.
 Activity calyces pelvis & ureter decreases
after 5- 10min.
 Delayed views beyond 30min is of little value
unless the patient has obstruction
 99mTc MAG3 & DTPA are similar
 99mTc GH & DMSA show progressive
accumulation delayed views will show better
images of the renal cortex after the
background & collecting system has
decreased
Renogram

 Initially renograms were performed with

multiple single crystal probes positioned over
the patients back, the tracer doses were 1ly
30mci
 Now a days Anger camera’s are used with
the patient seated in front of it upright
position
 Phase1 30sec – arrival of the injected tracer
at the blood pool of the kidney the activity
poorly related renal blood flow
 Phase2 4-6min terminals when activities
reaches maximum as the blood levels falls
rapidly the activity in the urine is maximum
initially & falls with time so the rate of
increase in count is directly related to the
renal blood flow & function & inversely
related to urine formation rate.
Fractionation of kidney function

 Slope method
 Intergrated count method
Slope method

 The slopes of 2 curves of the kidneys

between 60-150sec after injection calculated
& the 2 values are added together & the
fractional contribution of each kidney slope to
the total is calculated
Intergrated count method

 Counts for each kidney between 60-150sec

are added & the fractional contribution of
each kidney to the total is calculated
 When % are used they should add up to
100% these means if 1 kidney remains the
same after some time & the other improves
in clearance the 1 that remains same will
appear to have lost function
GFR

 99mTc DTPA fullfils the criteria

 I125 I131 can also be used
 GFR is computed by GFR=A(L+R)-B where
L& R are the renal uptakes where A &B are
constants
 Adv rapid dertmination of total & split renal
function with blood sampling mean value
130ml/min in men 120ml/min in women new
born 20-40 % of adult value at age 1=adult
 ERPF=A+B/S +C/S where A B C are
constants n S is the fraction of the injected
dose per ml at the 44min
ERPF

 Only a portion of renal blood flow is

presented to renal secretory tissues & no
substances perfusing the kidney will be
totally extracted so the calculated clearance
will be less than the total renal plasma flow
 PAH & OIH labeled with I123 &I131 are used
so images n fractional ERPF n total ERPF
are obtained
Nuclear cystography

 .3-1mCiof99mTc with 250-500ml of saline

thro a catheter
 Bladder slowly filled n sequential images
obtained.pt is asked to void.
 Frames at 15-30secs obtained.
 Reflux n its severity can be gauged by the
volume required to produce the reflux.
Scrotal imaging

 99mTc-20mCi is given iv .flow sequence

of3secs per frame at 70mm image size to
detect torsion
Clinical application- diagnostic

 ARF DTPA,MAG3 are recommended for

dynamic renal scintigraphy
 Flow portion is important for evaluating blood
flow
 Peak of activity in the kidney should not be
more than 3sec after the peak of aorta
 Intensity of activity should = or more than the
early activity in spleen
 Unilateral delay or visualization
 renal artery occlusion due to
thrombosis ,embolism or aneurysmal
dissection or severe unilateral ureteral
obstruction
 Bilateral delay – less specific
 ATN
 shock
 bilateral ureteral obtruction
Static images

 Should be symmetric n homogenous in renal

cortices
 With in 5min background activity lessens n
collecting system is visualized
 Bilateral normal sized kidney’s – recent on
set? Reversible
 Small kidney’s –chronic disease, irreversible
 Large kidneys –amyloidosis,RVT
 Asymmetry of up take + flow abnormality =
vascular problem
 Lack of uniformity – parenchymal scarring n
mass lesions
 Delay in up take- poor renal function
secondary-parenchymal disease. If severe
can decrease the flow
 In severely oliguric or anuric pt MAG3 I131
should be used because these will be
concentrated even with 3% of function
CRF

 MAG3 is ideal
Masses n pseudomassses

 Radiologic n radionuclide are complementary

 In pseudomasses the up take will be normal
or sometimes intense
 Cyst or infarct –no activity
 RCC early blood flow ,late photon deficient
Hydronephrosis n hydroureter

 MAG3 is used for infants otherwise DTPA

 3 curves are possible
 definite decrease in count with time after lasix- non
obstructive
 definite increase- obstructive
 plateau indeterminate
 poor renal function , large
hydronephrosis
 t1/2 less than 10min normal more than obstruction 10-20min
indeterminate. Full bladder delays the wash out.

Figure 1.2 Time activity curves of a typical renogram. Note the time
taken to reach maximum uptake; ~ 4 min. This patient had two good
functioning kidneys and a percentage uptake ratio of approximately 50:50
Figure 1.3 Renogram of patient with non-obstructive hydronephrosis.The
administration of the diuretic at ~ 15 min induced excretion, indicating the absence of a
mechanical obstruction.
Figure 1.4 Renogram of patient with obstructive hydronephrosis of the right
kidney.There is no excretory phase for the right kidney even after the administration of
the diuretic at 15 minutes. The cause of this patient’s hydronephrosis is mechanical.
VUR

 The grade n severity can be assessed

 PVR accurately known
 DMSA SPECT scans recommended
RAS

 Initial flow images – decreased perfusion on

the affected side with reduced concentration
n prolonged parenchymal transit time.
 Sensitivity 60-85%.
 25 -50mg captopril will increase the
sensitivity to more than 90%
 MAG3 n DTPA OIH are used
RVT

 Kidney enlarged
 Decreased flow
 Poor uptake
Transplant evaluation

 MAG3 is used
 Anterior images are taken
 Bladder –kidney ratio at 30min 3:1-5:1 with
hippurate or 10:1 with MAG3
 Native kidney function might give false
results
 Early p-o period upto 4 weeks
 Total absences of flow with photopenia
 Thrombosis of RA or RV hyperacute rejection
or severe obstruction
 Decreased early uptake with increasin
activity in later views n poor excretion seen in
ATN acute rejection obstruction this means
intact blood flow but decreased function –
tubular block
 As the kidney improves the count increases
in bladder to kidney ratio improves n the
curve starts peaking in the 1st 10min Failure
implies rejection
 Collection of tracers outside the urinary tract
imply leaks to differentiate from blood or
lymph
 Normal perfused transplant
 Activity appears in the graft within 6sec of itz
appearance in the iliac artery
 Maxi activity =or greater than the artery
 Clear fall after the peak
 Blood flow intact in ATN but decreasd in
rejection
Congenital anomalies

 Horse shoe kidney crossed fused ectopia n

ectopic kidney’s using DTPA n MAG3
 Non visualization- dysplastic
 Uniform cortical rim sign with graual filling of
PCS- hydronephrosis
Trauma

 MAG3 or DTPA are used to know whether

there is blood flow or not , extravasation n
obstruction
Scrotal imaging

 Increased tracer activity in inflammation

 Torsion 4 patterns
 normal if spontaneous detorsion within 4 hrs
 less than 7hrs no increase of perfusion.cold area
in the region of testis
 7-24hrs increased activity around the cold testis
due to hyperemia
 after24hrs symmetric intense hallow surrounding a
cold testis
 Tumour testis also increased perfusion which
is diffuse
Penile vascularity n impotency
evaluation
 Prostatic lymphoscintigraphy with
antimonysulfide when injected into prostate
glands will be traped by regional lymph
nodes
 Pedal lymphoscintigraphy for chyluria
Adrenal imaging

 NP-59 MIBG for hyperadrenalism n

phaeochromocytoma
Immunoscintigraphy

 With capromabpendetid reacts with psma

when labled with indium 111,so has been
used to detect extra prostatic disease
 It is superior to pet imaging to detect local
recurrence n lymph node meds
 Accuracy 92% for local disease n 80% for
extraprostatic
Brachy therapy

 Using an imaging modality such as ultrasonography,

MRI, or CT, temporary catheters that contain the
implants are positioned in the prostate. Patients
require hospitalization while the implants remain in
place but may go home once the implants are
removed. IMRT is usually used with this technique.
The optimal patient population has not yet been
determined. High dose rate brachytherapy is
commonly delivered in 2 or more fractions of 810 Gy
or more. Most series reported are from single
centers.
 Pd-103 (in combination with IMRT) as the
isotope of choice in the treatment of locally
advanced disease because of its higher dose
rate.
Studies of cesium (Cs)–131 in permanent
prostate brachytherapy have been increasing.
Cs-131 is an attractive alternative, as its
average energy is similar to that of I-125 and it
has a half-life of only 9.7 days.
 The most common isotope used for
temporary brachytherapy is iridium (Ir)–192,
which provides a higher dose of radiation
than the I-125 or Pd-103 permanent
implants. As such, the Ir-192 implants are not
left in the prostate gland.

Most brachytherapy for prostate cancer is performed using

the permanent technique, which is the focus of the
remainder of this article
 Contraindications
 Brachytherapy has several relative contraindications, as
follows:

 Transurethral resection of the prostate: Initially, prior

transurethral resection of the prostate was associated with
increased symptoms and urinary incontinence rates as
high as 50%, but more recent studies have reported
incontinence rates of less than 10%.
 .
 Pubic arch interference: Interference may
occur because of a large prostate (a gland
>40 g), and this interference may preclude
adequate placement of seeds. Hormonal
ablation, exaggerated lithotomy,
horizontal probe position, and CT-guided
placement are all potential solutions
 Obstructive symptoms: Significant preoperative
obstructive symptoms increase the likelihood of
postoperative urinary retention. While glands
larger than 40 g are more likely to have
obstructive symptoms, symptoms can occur in
anyone. Glands between 50 g and 60 g require
downsizing. Hormone ablation has been reported
to downsize the prostate gland by 25-40% and is
used to facilitate brachytherapy in patients with
large glands.
 One study randomized prostates of comparable
size to brachytherapy alone or brachytherapy
after hormone ablation.9 They found that the
acute side effects of urinary retention and
dysuria were actually greater in the hormone
ablation group. Clinicians often compromise and
use a 5-alpha reductase inhibitor rather than true
androgen ablation for downsizing. Nonetheless,
brachytherapy is not advisable in patients with
glands larger than 60 g.
 Morbid obesity: Focusing on the target is
feasible, but the equipment often cannot
sustain the weight or is not long enough
to reach the prostate.
Different isotopes have been used for brachytherapy of
prostate cancer. These include radon 222, cobalt 60,
radium 226, gold 198, iodine 125, palladium 103,
caesium 137, and iridium 192. As mentioned above,
these isotopes can be implanted temporarily and
permanently. Nowadays, the most commonly used
radioactive sources for the treatment of prostate
cancer are iodine 125 and palladium 103 as
permanent implants and iridium 192 as a temporary
implant.
 The common interstitial brachytherapy techniques
are high-dose rate (HDR), pulse-dose rate (PDR),
and low-dose rate (LDR). Interstitial brachytherapy
involves needle- or catheter-guided placement of
radioactive sources inside the organ of interest. The
LDR technique is not used in prostate cancer.
 HDR and PDR brachytherapy implies the local
placement of radioactive sources for a certain period
of time. The planned dose is administered by
keeping the source in place for a precisely calculated
time.
 This source is applied in one or more sessions, and
a reasonably high dose of radiation reaches the
target organ for a short duration of time; the
catheters or needles are removed at the end of the
procedure. In this technique, external-beam radiation
may accompany the implantation.
 Another technique involves permanent implants, in
which seeds remain in place for as long as the organ
remains in situ.
 Three radionuclides are currently approved
for the treatment of bone pain: first-
generation phosphorus-32 (32P), second-
generation strontium-89 (89Sr), and third-
generation samarium- 153 (153Sm). These
radionuclides all localize to regions of
enhanced bone turnover and deliver high
local doses of radiation through the emission
of beta particles.
 The mechanism of bone targeting varies for
each of them. 32P is targeted to bone
through inorganic phosphate pathways and,
in a similar manner, 89Sr is taken up as a
calcium analog. 153Sm, however, is the only
agent in its class targeted to bone via
chelation to the aminotetraphosphonate
EDTMP (ethylenediaminetetra-
methylenephosphonic acid).
 Samarium-153 is produced by the neutron
bombardment of isotopically enriched 152Sm2O3 in
a nuclear reactor. Soluble ionic 153Sm3+ when
administered intravenously has very little propensity
for bone, but when chelated by a variety of
aminocarboxylate and aminophosphonate ligands it
can be quite effectively targeted to the skeleton.
Goeckeler and colleagues18 demonstrated that the
complex formed with EDTMP had a combination of
biologic properties necessary for a bone-targeted
radiotherapeutic agent.
 These include rapid clearance from the vascular
compartment following intravenous injection, high
uptake and retention in the skeleton, and rapid renal
clearance and urinary excretion of the portion not
bound to bone. In addition, it was found that
localization of the complex to newly formed bone,
such as that laid down by osteoblastic bone
metastases, was 10- to 20-fold higher per gram than
that found in normal bone.
 188Re-HEDP for the palliative treatment of
bone metastases. Rhenium-188-HEDP has a
rapid renal excretion (40±12% of
administered activity within the first 8h),
leading to a low radiation dose to the whole
body (0.07±0.02mGyMBq−1) and a relative
short biological half-life (51±43h) in
comparison to the half-life within bone
metastases (269±166h) (Liepe et al, 2003)..
 The favourable physical characteristics of the
radionuclide for its use in palliative therapy
are a short physical half-life of 16.9h and a
maximal β-energy of 2.1MeV with a 15% γ-
component of 155keV. This γ-component
allows the control of tissue distribution after
therapy
 Radioactive Strontium 89 is a similar drug
to Samarium 153, but frequently only a single
course can be given due to bone marrow
effects.
 Phosphorus-32, employed as the
orthophosphate or polyphosphate, can
reduce or relieve the pain of osteoblastic
metastases without serious hematologic
toxicity, especially if used as a single
injection. Uptake of this beta-emitter by
osteoblastic-reactive bone and possibly by
tumor and other cells can lead to pain
reduction and often to cell killing.
 Thank you