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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
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
Gamma camera, 1950s
Planar imaging
99mTcO4Thyroid
scan131IWBS
99mTc-HEDPBone scan
Single photon emission
computed tomography (SPECT)
Hybrid imaging
SPECT/CT
Positron emission (b+)
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
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
PET-CT
Normal whole body FDG-
PET/CT studyMIP
Glucose uptake into tumours
GLUCOSE VS FDG
Extracellular
Intracellular
Glucose
Transporter
Hexokinase
ATP ADP
Glycolisis
Glu
P
FDG
P
GluGlu
Glu
GluGlu
Glu
FDG
FDG
FDG
FDG
FDG
FDG
FDG uptake
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
Lymphoma, staging
GIST, rapid response to imatinib
BRAF mutant melanoma
Day 0
Metabolic response!
Day 28
Pt. 6 Time to progression 1 mo
Day 7 Day 14
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
Lopci et al., Eur J Nucl Med Mol Imaging (2015) 42:597–612
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.
MOLECULAR RADIOTHERAPY:
Targeting the Sodium Iodide Symporter (NIS)
Diagnostic
agent
Therapeutic
agent123I, 131I, 99mTc 131I
Treatment of differentiated thyroid cancer
with 131I
May 2005
Ant Post
Sep 2005
Ant Post
Mar 2006
Ant Post
Jan 2007
Ant Post
Somatostatin receptor targeting
Neuroendocrine tumours
Octreotide
Late 1980s
111In-Octreotide
Early 1990s
Gamma camera
68Ga-DOTATOC/TATE
Early-mid 2000s
PET
Companion compounds
Radiometal
68Ga, 111In
Linker
Ligand
Chelator
Target
90Y
177Lub
213Bi
225Ac212Pb
a
Twenty-five years and counting….
177Lu-DOTATATE
mid-late 2000s
First proper RCT NETTER-1
final PFS analysis, NEJM 2017
Control Arm
Treatment Arm
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
J Nucl Med 2019; 60:801–805
