Radioisotopes in urology

ROLE OF RADIOISOTOPES IN DIAGNOSIS &
MANAGEMENT OF UROLOGICAL PROCEDURE
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai

MODERATORS:
Professors:
 Prof. Dr. G. Sivasankar, M.S., M.Ch.,
 Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
 Dr. J. Sivabalan, M.S., M.Ch.,
 Dr. R. Bhargavi, M.S., M.Ch.,
 Dr. S. Raju, M.S., M.Ch.,
 Dr. K. Muthurathinam, M.S., M.Ch.,
 Dr. D. Tamilselvan, M.S., M.Ch.,
 Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai.
2

RADIOISOTOPE
 The terms Radionuclide, Radioisotope, Radio Tracer or
Nuclear Imaging agent all refer to the radioactive
material that is used to make the nuclear medicine
images.
 These substances are molecules that contain
radioactive atoms.
 When those atoms decay, they emit energy in the form
of gamma rays or alpha or beta particles & they are
detected by the nuclear medicine camera.
3

HISTORY
 Cyclotron invention in
1931 by Lawrence and
Sloan.
 It accelerates charged
particles outwards from
the center of a flat
cylindrical vacuum
chamber along a spiral
path.
4

CYCLOTRON
5

HISTORY
 Discovery of fission reaction in 1938 with
production of Iodine-131.
 First used for evaluation of thyroid function with
I131.
 Diodrast studied forGU tract in 1950s but
disadvantage was significant hepatic uptake.
 In 1960 131I-ortho-iodo-hippurate (OIH) was
introduced.
6

HISTORY
 Development of various radiotracers such as
99mTc labeled to DTPA, DMSA, GHA, MAG3
have further developed the field.
 Development of SPECT and PET scans are
latest in the field.
7

SCINTIGRAPHY
 Scintigraphy (Latin scintilla, spark) is a
diagnostic test used in nuclear medicine,
wherein radioisotopes are taken internally and
the emitted radiation.
 This raditaion activity is captured by external
detector gamma camera to form two-
dimensional images.
 It is not like a X-ray/CT scan where external
radiation is passed through the body to form an
image.
8

WHY RADIOTRACER STUDIES
 Provides useful and often valuable
functional information that is not easily
available from other methods.
 Associated with lower absorbed radiation
dose and significantly lower morbidity than
with contrast assisted procedures.
10

 Scintigraphy does not damage the kidney, has
no lingering toxicity and is free from allergic
reactions.
 It is noninvasive, has minimal risk, minimal
discomfort, and allows determination of the
function of the kidney.
11

RADIO ISOTOPES
 They are helpful in diagnostic & management purpose.
 MC used in urology - compounds labeled with Tc99m
Ideal agent
 Should contain no particulate radiation.
 Shortest possible half life.
 Should emit a photon in the range of 100-300 keV, so
can be detected by gamma camera..
 Inexpensive.
 Easy to store.
12

RADIOISOTOPES…
13

RADIOISOTOPES IN RENAL FUNCTION IMAGING
14

OIH (ORTHOIODO HIPPURATE)
 First described in 1960s.
 Structurally related to PAH (para-amino-hippurate).
 Tubular secretion – 80%
 Glomerular filtration – 20%.
 Low rate of extra-renal handling (<2%)
 Dose: 0.002-0.004mCi/kg.
 Thyroid uptake can be blocked by Lugol’s iodine.
 Expensive when compared to other radiotracers.
15

99MTC-DTPA
 Technetium 99m-diethylene triamine pentaacetic acid
(99mTc-DTPA) is primarily a glomerular filtration agent .
 It is most useful for evaluation of obstruction and renal
function because it is excreted through the kidney and
dependent on glomerular filtration rate (GFR).
 It is less useful in patients with renal failure because
impaired GFR may limit adequate evaluation of the
collecting system and ureters.
 T1/2 = <12 min
 It is readily available and relatively inexpensive.
16

99MTC-MAG3
 Technetium 99m-mercaptoacetyl triglycine (99mTc-
MAG3) cleared mainly by tubular secretion.
 A small amount, approximately 10%, of MAG3 is
excreted by extrarenal , mostly by hepatobiliary
excretion.
 T1/2 = 6 hrs
 Because it is extensively bound to protein in plasma, it
is limited in its ability to measure GFR but is an
excellent choice for patients with renal insufficiency
and urinary obstruction.
17

99MTC-ETHYLENE DICYSTEINE
 Similar to MAG property (tubular secretion)
 Can be labeled at room temp
18

99MTC-DMSA
 Technetium 99m-dimercaptosuccinic acid (99mTc-
DMSA) is cleared by both filtration and secretion.
 99mTc-DMSA localizes to the renal cortex with little
accumulation in the renal papilla and medulla.
 Therefore it is most useful for identifying cortical
defects and ectopic or aberrant kidneys.
 99mTc-DMSA can distinguish a benign functioning
abnormality in the kidney from a space-occupying
malignant lesion, which would not have normal renal
function.
19

RADIONUCLIDES
 Three basic classes of radionuclide for kidney
function & structure:
 Filtered agents : DTPA and MAG3
 Excreted agents : MAG3 and Hippuran,EC2
 Cortical imaging agents : DMSA and
Glucoheptonate
20

FILTERED RADIONUCLIDES
 DTPA ,MAG3 are filtered through the glomerulus. This is
useful in evaluating:
 Perfusion
Vascular supply
 Filtration
Measuring renal function (GFR)
 Drainage
Detects obstruction
21

EXCRETED RADIONUCLIDES
 MAG3 and Hippuran, EC2 are excreted by the
renal tubules. These radionuclides are helpful in
evaluating patients with:
 Diminished renal function
 Kidney transplants
22

CORTICAL IMAGING RADIONUCLIDES
 DMSA and Glucoheptonate are accumulated in
the cortex so they are helpful in evaluating:
 Renal scarring from chronic
infection
 Infarction
 Renal mass
 Differential renal mass
23

RADIO ISOTOPES IN RENAL INFECTION IMAGING
 Infection suspected–
 99mTc- DMSA,
 Ga 67- citrate bind to transferin
 Leucocyte labeled with 111 In- oxine
 Leucocyte labeled with 99mTc-HMPAO(Hexa-methyl-
prpylenemine –oxime)
 95-100% sensitivity for DMSA in acute pyelonephritis
 Cannot distinguish infection from sterile inflammation
24

25

67 GA - CITRATE
 It bind to transferin and transported to area of
inflammation in the body.
 67Ga T1/2 = 78.3 hours ,
 68Ga t1/2 = 68 min
 Single photon emission tomography (SPECT) fused
with CT- markedly improved lesion localization
 Gallium in the kidneys can persist up to 24 hours - can
obscure renal infection.
 So Imaging is taken after 48 hours.
 67Ga- citrate lacks specificity, uptake can be taken by
many neoplastic process. 26

111 INDIUM- OXINE
 For leucocyte labeled 111Indium-oxine imaging:
1. 50 mL of blood
2. labeling with tracer
3. reinjection
 Normally accumulate in liver, spleen & bone
marrow
 Other side uptake indicate presence of active
infection
 T1/2 = 67.3 hours
 Imaging with 111indium WBC - 24 hours
27

99MTC-DTPA
 Most widely used radiopharmaceutical agent
for imaging of kidney infections.
 Decreased uptake in areas of active
pyelonephritis.
28

99M TC DMSA
29
99mTc-DMSA scan
shows a focal wedge-shaped abnormality in the
upper pole of the left kidney consistent with Acute
Pyelonephritis

IMAGING OF GU MALIGNANCIES
30

18FDG
 Most commonly performed using the PET
radiotracer 18 FDG.
 18FDG – uptake by metabolic active organs
including brain , kidney.
 Additionally taken up by malignant cells by
aerobic glycolysis (Warburg Effect)
31

MECHANISM OF 18 FDG UPTAKE
 Malignant cells have
increased glucose
utilisation due to
 Over expression of
membrane glucose
transporter receptors,
especially GLUT1 & GLUT3
on surface of tumor cells.
 Increased hexokinase
activity
 Decreased level of G-6-
Phoshotase
32

KIDNEY CANCER
 18F- FDG PET
Highest sensitivity for papillary RCC type II with
metastasis.
 124I – girentuximab
target Carbonic anhydrase IX (CAIX)
CAIX universally expressed by clear cell RCC
 99mTc – sestamibi
Bind with high mitochondrial content
Bening oncocytoma, parathyroid adenoma
33

34
Differentiation of a localized clear cell RCC (A to C) from a benign renal oncocytoma (D to
F) using 99mTc-sestamibi SPECT/CT.
(A) CECT -heterogeneous mass in the left kidney . (B)Axial 99mTc-sestamibi SPECT (C)
axial 99mTc-sestamibi SPECT/ CT - NO radiotracer uptake. On HPE resected mass -
clear cell RCC.
(D) CECT - left-sided heterogeneousrenal mass (E)Axial 99mTc-sestamibi SPECT .(F)
axial 99mTc-sestamibi SPECT/CT - show intrinsic/highest radiotracer uptake, in those
parts of the mass (red arrowheads).On HPE resectedrenal mass biopsy confirmed as

BLADDER CANCER
FDG-PET
 Limitation- because excreted in urine
 Not detect micromets
Indication:
1. equivocal conventional imaging
2. metastatic lesions , those recurring in bed after
cystectomy
C11 choline- not excreted in urine
35

PROSTATE CANCER
HISTORY:
 The first radiotracer to be approved by the FDA specifically for
prostate cancer imaging was 11C-choline .
 This agent has been shown to provide added value over
conventional imaging in the detection of -occult pelvic lymph
nodes in patients undergoing radical prostatectomy.
 11C-choline that have been studied for prostate cancer
imaging, including 18F-fluorocholine, 18F-fluoromethylcholine,
and 11C-acetate but giving false positive result.
36

Current and new agents undergoing clinical study for radionuclide
imaging of PCainclude:
 2-18F-fluoro-2-deoxy-D-glucose (FDG)
 111In-7E11 antibody(ProstaScint™)
 18F-fluorodihydrotestosterone (18F-FDHT)
 radioacetateanalogs
 radiocholine analogs
 anti-1-amino-3-18Ffluorocyclobutane-1-carboxylic acid(anti-
[18F]FACBC)
37

RADIOTRACERS FOR PROSTATE CANCER
IMAGING
38

FDG PET
FDGwas not useful in:
 Detection of primary organ confined /early stage prostate cancer
 To differentiate post operative scar and local recurrence
However, FDGis usefulin:
 detecting bone and soft-tissue PCametastases, although it is less sensitive
than bonescan
 It has also been shown that FDGuptake correlates with elevated
prostate-specific antigen (PSA) levels and the rate of increase in PSAasa
measure of metastatic diseaseprogression
 From these results it has been suggested that FDGis useful for imaging PCa
in selected populations of patients with aggressive disease
39

18F-FACBC
(ANTI-1-AMINO-3-18F-CARBOXYLICACID)
 FDA approved radiotracer.
 Also known as 18F-fluciclovine
 18F-FACBC functions as a substrate for the amino acid
transporters LAT1(L-type AA transporter) and ASCT2( alanine-
serine-cysteine transporter 2), which are overexpressed by
multiple malignancies including prostate cancer.
 Useful in suspected prostate cancer recurrence on elevated
PSA level.
40

PSMA TARGETED RADIOTRACERS
 Early - 68Ga-labeled
agents (e.g., 68Ga-PSMA-
11 and 68Ga-PSMA-I&T),
 Now -18F-labeled
compounds (e.g., 18F-
DCFPyL and 18F-PSMA-
1007) that take advantage
of this radionuclide’s
longer half-life and
superior imaging
characteristics.
41

18F- DCFPYL
42
Imaging studies of a patient with metastatic prostate cancer. (A) 99mTc-MDP
(methylene diphosphonate) bone scan demonstrates intense radiotraceruptake
at a focus near the left sacroiliac joint (red arrowhead).(B) Axial, CE-CTimage- a
sclerotic lesion in the left iliac that corresponds to the site of uptake on the bone
scan (red arrowhead). (C) Axial 18F-DCFPyLPSMA-targeted PET and (D) 18F-
DCFPyL PET/CT fusion images demonstrate intense radiotracer uptake at the
same location (red arrowheads),corroborating the findings on bone scan and
CT.

68GA-RM2
 Gastrin-releasing peptide receptor (GRPR), which
is overexpressed in many human malignancies
including prostate cancer.
 68Ga-RM2 is a synthetic bombesin receptor
antagonist targeting gastrin-releasing peptide
receptors (GRPr) .Peptide derivatives of bombesin
bind to GRPR with high affinity.
 Radionuclides have been used to label bombesin
derivatives, including 18F, 68Ga, and 64Cu.
43

INDIUM (111IN) CAPROMAB PENDETIDE
(PROSTASCINT)
 Capromab is a mouse monoclonal
antibody which recognizes a protein found
on both prostate cancer cells and normal
prostate tissue. It is linked to pendetide, a
derivative of DTPA.
 Pendetide acts as a chelating agent for
the radionuclide indium-111.
 Following an intravenous injection of
Prostascint, imaging is performed
using single photon emission computed
tomography (SPECT).
44

18F- FDG
 Squamous cell carcinoma of the penis &
inguinal LN staging
 Recurrence of Seminoma & Non seminomatous
GCT
45

MIBG
 Metaiodobenzylguanidine (MIBG)
scintigraphy
 Using 123I or 131I
 Detection of ectopic pheochromocytomas-
gold standard
 Metastatic or locally recurrent disease
 Focal areas of increased MIBG activity
 Sensitivity less than 90%
 Specificity exceeds 90% if correlated with
CT or MRI
46

MALE INFERTILITY
 Penile scintigraphy
 By using RBC labeled Tc99m.
 To evaluation of penile blood flow for erectile
dysfunction
 Radiological evaluation of priapism
47

RADIONEUCLIDE CYSTOGRAM
 Sensitive in detecting reflux
 Significant lower absorbed
radiation
 Use
1. Follow up of documented
reflux
2. Screening siblings of children
with reflux
 Agents–DTPA, sulfur colloid,
pertechnate [ preferred],
MAG3
48

RADIOISOTOPES FOR MANAGEMENT OF
MALIGNANCY
49

HISTORY
 Prostate cancer
 Pasteau (1913) first described radium containing needles in
to prostate through urethra
 Huge Hampton Young (1922)- prostate brachytherapy by
using intracavitary radium sources in bladder, rectum &
urethra.
 Benjamin Barrington pioneered for – implanting radon gas
containing needles in to the prostate by transperineal
approach.
50

Brachytherapy is a method of treatment in
which sealed radioactive source are used to
deliver radiation at a short distance by
various methods.
 It developed largely through the use of
sealed radium and radon sources.
 In the 1950s, alternative artificially
produced nuclides became available.
 Gradually radium and radon were
replaced with 137Cs, 192Ir, 60Co, 198Au,
and 125I sources
51

52

DIFFERENT DOSE OF BRACHYTHERAPY
Ultra LDR : 001 to 0.3 Gy/hr : dose rate used in
permanent implants with I125 and Pd103
LDR : 0.4 to 2 Gy/hr, compatible with conventional
manual or automatic after loading technique
MDR : 2 – 12 Gy/hr, can also be delivered by manual or
automatic after loading, although the latter is far more
frequent
HDR : >12 Gy/hr and only automatic after loading can be
used because of the high source activity
PDR : pulses of 1 to 3 Gy/hr, delivers the dose in a
large number of small fractions with short intervals
Permanent Implants : deliver a high total dose
53

 LDR Interstitial Brachytherapy
1.Classical LDR permanent brachytherapy
 Radon 222
 Au 198 seeds
2.ULDR brachytherapy
low energy emitters –Pd103 and I125
LDR intracavitary brachytherapy
 Average photon energy : 60 to 100 keV
 Sources : Radium226 and Cesium137
54

PULSE DOSE RATE
 Combined physical advantage of HDR BT and
radiobiological advantage of LDR BT
 advantages of PDR brachytherapy compared with LDR
 full radiation protection for caregivers
 no source preparation necessary
 no extensive source inventory, that is, only one iridium-
192 source per after loader to be replaced every 2 or 3
months
55

1) Low dose rate: permanent implant
2)High dose rate : Temporary catheter
56
Radio isotopes Half life Energy emission
103 pallidium 21 d 21 kev
125 Iodine 59.6 d 28 kev
131 Cesium 9.7 d 30 kev
198 Gold 2.7 d 412 kev
222 Radon 3.83 d 83 kev
Radioisotpes Halflife Emissionenergy
192 Iridium 74 d 400kev

PALLIATION OF BONE PAIN IN CANCER PATIENTS
 Radiopharmaceutics - available for
reduction of metastatic bone pain
 Duration of response - few weeks to a few
months
Radiopharmaceutics are commercially
available (beta emitters):
 Sodium phosphate (32P)
 Strontium-89 chloride (89sr)
 Samarium-153 (153sm).
Now alpha emitters – radium 223 improve
bone pain in mCRPC with improve overall
survival
57

58

SODIUM PHOSPHATE (32P)
 Since the 1950s
 Radioactive phosphate is incorporated into
hydroxyapatite
 Good response rates, 60% to 85%
 Advantages of 32P
1. Oral
2. Does not have to be sterile or completely free of
pyrogens
3. Low expense
59

STRONTIUM-89 CHLORIDE
 Silberstein and colleagues
 Overall response rate of 25-65%
 Half life 4-5 days
 Beta emitter
 Retention is longer , lead to myelotoxicity
 Amount of response directly proportional to the
administered dose
 Use: castration resistent prostate cancer bone
pain
60

SAMARIUM-153-ETHYLENE DIAMINE
TETRAMETHYLENE PHOSPHONATE
 Binds hydroxyapatite
 Response rates of 55% to 80%
 Half life 2 days
 No additional effects demonstrated at higher doses
 Primary adverse reaction - myelotoxicity
 Fatalities if using both 89sr and 153sm
 Result of severe thrombocytopenia
 Initial 48 to 72 hour increase in pain- ‘‘flare phenomenon,’’
 Associated with a therapeutic palliative response.
61

Thank you.....
62

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