oncological imaging: radionuclide techniques
TRANSCRIPT
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What can we imageParticle
mass
Range
(H20)Imaging
a 4 µm No
b 0.0005 mm Indirectly
b+
(positron)0.0005 mm PET
g 0 m
Gamma
camera/
SPECT
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T1/2 (h) Eg (Kev)
99mTc 6.03 140111In 72 171-245
81mKr 13 (s) 190
131I 8.02 (d) 364123I 13.2 127
67Ga 78 93-184-300201Tl 73 135-167
Gamma emitting radionuclides
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Gamma camera, 1950s
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Planar imaging
99mTcO4Thyroid
scan131IWBS
99mTc-HEDPBone scan
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Single photon emission
computed tomography (SPECT)
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Hybrid imaging
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SPECT/CT
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Positron emission (b+)
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PET radionuclidesT1/2 (min) Eb
+ (kev)
11C 20 96013N 10 119015O 2.05 172018F 109.6 635
82Rb 1.3 3350
68Ga 68 1900124I 4.2 (days) 214094mTc 52 247076Br 966 398064Cu 762 571
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Advantages over gamma camera
– Intrinsically Tomographic
– Quantitative (KBq/ml)
– Very high sensitivity
– Dynamic studies and kinetic
modelling (pmol/min/g)
– Higher spatial resolution
– High specific activity ligands
• FDG ≈ 50-500 GBq/µmol (EOS)
• Typical patient dose ≈ 300 MBq
• Injected mass ≈ 1 nmol
• Glucose 5.5 mM in plasma
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PET-CT
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Normal whole body FDG-
PET/CT studyMIP
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Glucose uptake into tumours
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GLUCOSE VS FDG
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Extracellular
Intracellular
Glucose
Transporter
Hexokinase
ATP ADP
Glycolisis
Glu
P
FDG
P
GluGlu
Glu
GluGlu
Glu
FDG
FDG
FDG
FDG
FDG
FDG
FDG uptake
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Going way back
• FDG in Glioma (early
1980s)
– Di Chiro et al. Neurology,
1982, Vol.32 (12), p.1323
– Grading
– Residual disease vs
necrosis
– Recurrence vs necrosis
– The magic bullet
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Lymphoma, staging
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GIST, rapid response to imatinib
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BRAF mutant melanoma
Day 0
Metabolic response!
Day 28
Pt. 6 Time to progression 1 mo
Day 7 Day 14
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Limitations of FDG
•Poor target to background ratios in tissues
with high physiological FDG uptake
– Brain tumours
•Non FDG avid tumours
– Well differentiated Neuroendocrine Tumours
– Prostate cancer
– others
•Specificity: Inflammation, Infection
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Lopci et al., Eur J Nucl Med Mol Imaging (2015) 42:597–612
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Theranostics
(a portmanteau of therapeutics and
diagnostics) is a proposed process of
diagnostic therapy for individual patients -
to test them for possible reaction to taking
a new medication and to tailor a treatment
for them based on the test results.
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MOLECULAR RADIOTHERAPY:
Targeting the Sodium Iodide Symporter (NIS)
Diagnostic
agent
Therapeutic
agent123I, 131I, 99mTc 131I
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Treatment of differentiated thyroid cancer
with 131I
May 2005
Ant Post
Sep 2005
Ant Post
Mar 2006
Ant Post
Jan 2007
Ant Post
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Somatostatin receptor targeting
Neuroendocrine tumours
Octreotide
Late 1980s
111In-Octreotide
Early 1990s
Gamma camera
68Ga-DOTATOC/TATE
Early-mid 2000s
PET
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Companion compounds
Radiometal
68Ga, 111In
Linker
Ligand
Chelator
Target
90Y
177Lub
213Bi
225Ac212Pb
a
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Twenty-five years and counting….
177Lu-DOTATATE
mid-late 2000s
First proper RCT NETTER-1
final PFS analysis, NEJM 2017
Control Arm
Treatment Arm
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T1/2 = 10 days, 4 a decays
J Nucl Med 2017; 58:1624–1631
• 14 patients
• Dose escalation
• Heavily
pretreated
• 8 pts multiple Rx
• 9/11 pts objective
response
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J Nucl Med 2019; 60:801–805