Seeing and Believing: Medical i
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Isotopes in Functional p
Cancer Imaging
François Bénard, MD, FRCPC
BC Cancer Agency and BC Cancer Agency
and
University of British Columbia
Nuclear Medicine 101
Nuclear Medicine 101
• A
A radioactive atom
radioactive atom is produced in a nuclear
in a nuclear
reactor (fission, neutron enrichment) or cyclotron (using protons, deuterons or alpha particles)
• This radioactive atom is coupled to a carrier molecule in most cases
• The radioactive compound is administered to patients (intravenous, orally, intradermal, inhaled)
A brief history of Nuclear Medicine
• 1930s: Discovery of artificial isotopes, notably Iodine‐131 and Tc99m
• First treatment in 1939 with phosphorus‐32
• First treatment with iodine‐131 in 1946
• Gamma camera (Anger) and Rectilinear Scanner (Cassen) in 1950s
• Thyroid imaging 1950‐1960
• Liver/spleen scanning, bone imaging, brain tumour localization
1960‐1970s
Positron emission tomography in 1970s+ for brain
in 1970s+ for brain imaging
• Positron emission
• Cardiac imaging 1980s+
• Cancer imaging
g g in the 1990s and beyond
y
Some definitions
• SPECT: Single photon emission
S C : S g e p oto e ss o co
computed
puted
tomography
– Three dimensional images acquired from the single photon emission produced by gamma emission decay
– Typical isotopes: Tc‐99m, In‐111, Tl‐201, I‐123,…
• PET: Positron emission
PET P it
i i tomography
t
h
– Three dimensional images acquired from the dual photon emission produced by the annihilation of a photon emission
by the annihilation of a
positron
– Typical isotopes: C‐11, F‐18, Ga‐68, O‐15, Rb‐82, …
Technetium‐99m, the medical isotope of the 20th century
f h
h
• Element 43 discovered by Carlo Perrier and Emilio Segrè in 1936 • Technetium‐99 discovered by Seaborg and Segrè at the erkeley Radiation aboratory
Segrè at the Berkeley Radiation Laboratory
• BNL, 1950s: Tucker and Green developed the first 99Mo/99mTc generator
• BNL, 1960: Powell Richards, presented the BNL 1960 P
ll Ri h d
t d th
first paper on the generator.
• Richards met with Paul Harper on the flight to Rome and spent the flight “extolling the merits of 99mTc”
In part from http://www.bnl.gov/bnlweb/history/Tc‐99m.asp
Single photon emitters in Oncology
111In Pentetreotide
for neuroendocrine cancers
99mTc MDP Bone Scan
99mTc Sulfur Colloid 99mTc Sestamibi
Sentinel Node Detection
Breast Cancer Detection
How many tests are done in Nuclear Medicine?
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d
• 30,000 diagnostic tests per week using radiopharmaceuticals in Canada
• 30,000‐40,000 tests per day in USA
• 80
80‐90%
90% use technetium
use technetium‐99m
99m
PET imaging 101
Molecular imaging: b
beyond imaging the structure
d
h
• Traditional
Traditional imaging methods use differences in imaging methods use differences in
organ morphology, appearance to make a diagnosis
• Functional imaging methods use radioisotopes and contrast agents to look at organ function
and contrast agents to look at organ function
• Molecular imaging methods use specific probes (usually radioactive) to measure b (
ll di
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biochemical processes and proteins
Example: Glucose metabolism
Example: Glucose metabolism
• Many oncogene
y
g
pathways increase glycolysis
p
y
gy y
by cancer cells (particularly PI3K/Akt pathway)
• Utilization of glucose increases markedly
Utilization of glucose increases markedly
• 18F‐FDG (Fluorodeoxyglucose) is a glucose analogue that is trapped in cancer cells in
analogue that is trapped in cancer cells in proportion to glucose utilization
• Discovered in a US government laboratory
Di
d i US
tl b t
• Used in cancer diagnosis worldwide
Staging Cancer with PET/CT
Response to experimental drugs
Baseline
1 month after onset of
therapy
Cancer Imaging Targets BCCA/TRIUMF
Imaging hormone receptors
Imaging hormone receptors
• “Receptors”
Receptors are proteins expressed in cells to are proteins expressed in cells to
which a hormone or drug will bind
• Estrogen receptors are expressed in 80% of receptors are expressed in 80% of
breast cancer and stimulate cancer growth
• The pathologist will look for these receptors Th
h l i
ill l k f h
when examining a biopsy
• What happens when the cancer spreads elsewhere?
Are tumours all the same
within a given
a given patient?
Proven inguinal breast cancer metastases, some with increased FDG uptake but no FES uptake (arrow). 18F‐FDG PET scan, top row; 18F‐FES PET scan, bottom row
Canadian Cyclotron Infrastructure
Canadian Cyclotron Infrastructure
• 18 Cyclotrons in Canada in 12 facilities
– 6 in Vancouver
– 2 each in Hamilton, Toronto, Montreal
– 1 in Edmonton, Winnipeg, London (ON), Ottawa, Sherbrooke, Halifax • 7 new cyclotrons planned or purchased
– Edmonton, Saskatoon, Toronto, Thunder Bay, y
Montreal, Sherbrooke, St‐John
W ld id O
Worldwide: Over 350 cyclotrons in 2006
350
l
i 2006
Can Cyclotrons help prevent isotope shortages?
h
• Distribution model established for 18F‐
Fluorodeoxyglucose (110 min half‐life)
• Mixed model possible for 18F (1 h irradiation) p
(
)
and 99mTc production (3‐6 h irradiations)
• Take advantage of existing infrastructure
• Proof of concept established in 1971 (Beaver Proof of concept established in 1971 (Beaver
and Hupf)
Challenges for cyclotron production of Tc99m
Calculate theoretical yields
l l
h
l ld
Target Preparation
Designing new targets for existing cyclotrons
Technetium extraction/isolation
100Mo recycling
y g
99mTc
Assess impact on patient dosimetry
Purification
Assess practical usable yields
Assess practical usable yields
Impact of other Tc Radioisotopes
on Patient Absorbed Dose
b b d
Hou X, Celler A, Grimes J, Benard F, Ruth T. Phys Med Biol 2012; 57: 1‐17.
Other Cyclotron Isotopes of Interest
Other Cyclotron Isotopes of Interest
•
•
89Zr (t½ 78.4 h), to label proteins and antibodies
68Ga (t½ 68.3 min) and 44Sc (t½ 3.93 h), the technetium replacements of the future?
94 Tc (t½ 53 min), the positron emitting technetium
• 94m
(½
i ) h
i
i i
h i
• 86Y (t½ 14.74 h), a diagnostic counterpart to 90Y used in therapy
• 11C (t½ 20.4 min), if only there was a cyclotron in every hospital!
Can all be produced by small cyclotrons < 10 MeV
Conclusion
• Cyclotrons provide us with medical isotopes that play a critical role in:
play a critical role in:
– Understanding Cancer Biology
– Diagnosis and Staging of Cancer
Diagnosis and Staging of Cancer
– Monitoring response and Personalizing the treatment approach
• A large number of existing cyclotrons are capable of securing Tc99m supply
• Many other useful isotopes can be produced by small medical cyclotrons
Thank You!
Thank You!
• Institutions:
Institutions: TRIUMF, BCCA, UBC, Lawson TRIUMF, BCCA, UBC, Lawson
Research Institute, McMaster University
• Collaborators:
Collaborators: – T. Ruth, P. Schaffer, K. Lin, A. Celler, S. Zeisler, E. Asselin, D. Perrin, S. Aparicio, S. Dedhar, D. Yapp, B. Guérin., D. Wilson
• Staff and Students: – K. Buckley, J. Klug, V. Haanemayer, F. Mesak, M. Vuckovic, J. Greene, T. Morley, JP Appiah, X. Hou, M Pourghiasian G Dias J Lau J Pan P Tsao
M. Pourghiasian, G. Dias, J. Lau, J. Pan, P. Tsao