1. Nuclear Medicine Physics
Radioactivity and Radioactive Decay
Radionuclide Production
Jerry Allison, Ph.D.
Department of Radiology and Imaging
Medical College of Georgia

2. Medical College of Georgia And Sameer Tipnis, Ph.D.
A note of thanks to
Z. J. Cao, Ph.D.
Medical College of Georgia
And
Sameer Tipnis, Ph.D.
G. Donald Frey, Ph.D.
Medical University of South Carolina
for
Sharing nuclear medicine presentation content

3. A Review Nuclear decay rules Based on conservation laws
-decay: AXZ  AYZ+1 + e- + ~
-decay: AXZ  AYZ-1 + e+ + 
e-capture: AXZ + e-  AYZ-1 + 
-decay and internal conversion: no changes for A & Z

4. Nuclear decay scheme +-decay and EC (electron capture)
F18 (FDG): cancer, myocardial disease, etc.
Sometimes drawn with vertical drop of 1.02 MeV for positron emission (rest mass equivalence of 2 electron electron masses)
Also Rb 82 for myocardial imaging

5. Nuclear decay scheme EC (electron capture)
Ga67 (gallium citrate): tumor localization
Ga-67 used in tumor localization
Also In-111, I-123, I-125 and Tl-201
No beta to contribute to dose

6. Nuclear decay scheme
--decay
I131 (NaI): thyroid disorders and cancer

7. Nuclear decay scheme
-decay
Tc99m (various compounds): various uses

8. Following - and + decay and Electron Capture
g-ray emission or internal conversion follows if the child nucleus is in an excited state
Any resultant electron vacancies are resolved through emission of characteristic X-rays and/or Auger electrons (radiation dose with no imaging benefit)

9. Question Match the decay mode to the description below:
A. beta minus decay
B. beta plus decay
C. alpha decay
D. isomeric transition
  1. Ra-226 to Rn-222
2. Z increases by 1
3. Z decreases by 1
4. Z decreases by 2
5. A and Z remain constant
6. tritium (H-3) to helium (He-3)
7. Tc-99m to Tc-99
8. Electron capture can be a competing mode of decay
A to 2
A to 6
B to 3
B to 8
C to 1
C to 4
D to 5
D to 7

10. Radioactivity : decay constant with units of 1/sec or 1/hr
A (t): disintegration rate at time t (decays/sec)
N(t): number of nuclei at time t
: decay constant with units of 1/sec or 1/hr
 = ln2/T1/2 = 0.693/T1/2
half life: T1/2 = ln2/ = 0.693/

11. Radioactivity
unit in SI: 1 Bq = 1 disintegrations per second (Becquerel)
traditional unit: 1 Ci = 3.7×1010 dps (1g of Ra-226, extracted first by Mme. Curie)
1 mCi = 37 MBq
NM imaging: ~ 1 to 30 mCi (30 – 1100 MBq)

12. Question
How many F-18 atoms are there in 10 mCi of FDG? (T1/2 = 110 min) A. 3.5 × 1019 B. 3.5 × 1016 C. 3.5 × 1012 D. 3.5 × 109 E. 3.5 × 106
A = lN
N = A/l
A = 10×3.7×107/s
= 0.693/(110×60s)
N = A/l = 3.5×1012

13. Radioactivity
decay equation: A(t) = A0 exp(-t)

14. Physical Half-life (Tp)
Tp = time required for the number of radioactive atoms to reduce by one half
Basic equations:
Nt = N0e-t or At = A0e-t
Tp = / 
 = / Tp
N0 = Initial number of radioactive atoms
Nt = number of radioactive atoms at time t
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

15. Physical Half-life (Tp)
Tp = time required for the number of radioactive atoms to reduce by one half
Basic equations:
Nt = N0e-t or At = A0e-t
Tp = / 
 = / Tp
N0 = Initial number of radioactive atoms
Nt = number of radioactive atoms at time t
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

16. 8 t1/2  ~ 0.4%
10 t1/2  ~ 0.1%
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

17. A0 = 500 Ci ; t = 2 days = 48 hr; Tp = 67 hr
A pt is injected with 500 Ci of 111In (Tp = 67 hrs). The patient is imaged 2 days later. Assuming none of the activity is excreted, what is the remaining activity at the time of imaging?
A0 = 500 Ci ; t = 2 days = 48 hr; Tp = 67 hr
At = A0e-t
 = 0.693/Tp = 0.693/67 hr = hr-1
t = hr-1 x 48 hr =  0.5
At = 500 Ci x e-0.5 = 303 Ci
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

18. Indium In-111 decays by electron capture to cadmium Cd-111 (stable)
Physical half-life of hours (2.81 days).
Photons useful for detection and imaging are:
Gamma 2, 90% abundant, 171 keV
Gamma 3, 94% abundant, 245 keV
Marketed as ProstaScint by Mallinckrodt for imaging of prostate cancer cells
Also used to label white blood cells for detection of inflammation

19. Biologic Half-life (Tb)
Tb = Time taken to reduce the amount of radiopharmaceutical in the body by one half due to various clearance mechanisms (excreta, perspiration, etc.)
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

20. Effective half life
Te = Time to reduce radiopharmaceutical in the body by one half due to functional clearance and radioactive decay
𝟏 𝐓𝐞 = 𝟏 𝐓𝐩 + 𝟏 𝐓𝒃
Te = 𝐓𝐩𝐓𝐛 𝐓𝐩+𝐓𝐛
if Tp >> Tb, Te ≈ Tb
if Tp << Tb, Te ≈ Tp

21. A pt is injected with 100 mCi (Tp = 8 days; Tb = 4 days )
A pt is injected with 100 mCi (Tp = 8 days; Tb = 4 days ). What is activity in the pt after 8 days?
Te = TpTb/Tp+Tb = 2.67d
= / Te = / 2.67 d = 0.26 d-1
 t = 0.26 d-1 x 8 d = 2.1  2.0
A0 = 100 mCi
At = A0e-t
At = 100 mCi x e-2 = 13.5 mCi
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

22. Radioisotope production
Fission (Reactor produced)
99Mo, 131I, 133Xe
Cyclotron produced
Neutron activation (Reactor produced)
Generator: transient equilibrium
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

23. Cyclotron-produced radionuclides
for PET:
11B(p,n)11C
15N(p,n)15O
16O(p,a)13N
18O(p,n)18F
for gamma camera:
111Cd(p,n)111In p
11B
11C n

24. Biosynthesizer (hot cell)
Used to attach the cyclotron-produced radionuclide to a biological compound, e.g. F-18 to FDG (2-deoxy-2-[18F]fluoro-D-glucose)

25. Biosynthesizer (hot cell)

26. Neutron activation
Samples bombarded with the large neutron flux in a reactor
14N(n,p)14C
23Na(n,g)24Na
31P(n,g)32P
124Xe(n,g)125Xe  125I
130Te(n,g)131Te  131I

27. Parent-daughter decay schemes
Transient equilibrium: Tp > Td
99Mo42  99mTc43 + e- + 66 h %
99mTc43 99Tc43 + 6 h
They decay in parallel after tmax to achieve equilibrium.
tmax= 24 hr for Mo-Tc equilibrium
𝑨𝒅(𝒕) 𝑨𝒑(𝒕) = 𝑻𝒑 𝑻𝒑−𝑻𝒅 (1.1 for 99mTc/99Mo)
𝑨𝒅(𝒕)/𝑨𝒑 𝒕 = 1.1 for 99mTc/99Mo which times the branching ratio of for MO-99 -> so Tc-99m is 3.6% below Mo-99 at equilibrium

28. Transient equilibrium
1.1 x .876
For 99mTc,
Max yield ~ 24 hrs
~3 Curies of Mo99
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

29. Generator-produced radionuclides
produce radionuclides using different chemical properties between the parent and child
parent T1/2 child decay T1/ Sr d Rb b+,EC 1.3m Mo h mTc IT h

30. Nuclear decay scheme 99Mo42  99mTc43 + e- +  (87.6%)
99mTc43  99Tc43 +  1 4 2 . 7 k e V 5 9 T c 3 g % 8 I C
(6.01 h) m
(2.111x105 y) g1

31. Transient equilibrium is the basis of:
Mo-99 -> Tc99m generator
and
Sr-82 -> Rb-82 generator
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

32. Tc-99m generator
components: alumina column, lead shield, air filter, saline eluent
MoO4-- bound to alumina (Al2O3) but mTcO4- not strongly bound
eluted with 5 to 25 ml
saline: ~ % 99mTc
washed out in one
elution
Molybdate; Dioxido(dioxo)molybdenum

33. 99mTc generator Molybdate; Dioxido(dioxo)molybdenum
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

34. Tc-99m generator maximum activity available at 24 hr
usable activity available every 3 to 6 hr
Commercial generators are sterilized, shielded,
and largely automated.
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps, 4th edition, 2012

35. Tc-99m generator
Mo-99 decays to Tc- 99m 87.6% of the time (decays directly to ground state of Tc % of the time)
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps, 4th edition, 2012

36. 99mTc yield 99Mo generator typically delivered weekly
A ~ 1 to 2 Ci
Maximum 99mTc yield ~ 24 hours
About ½ of Max. 6 hrs after elution
As the week progresses Mo decays and Tc yield goes down
Eg. Monday:1.5 Ci of 99Mo (new generator)
Monday yield: 1.2 Ci of 99mTc in 10 mL eluate
Friday yield : ~ 0.5 Ci of 99mTc in 10 mL eluate
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

37. Major impurities from the generator
The eluate from a generator contains Tc- 99m and possibly tiny quantity of Mo-99. Also a small quantity of Al+++ may come out with eluate.

38. 99mTc QC
Goal – to have the least amount of contaminants (Mo, alumina) in the eluate
99Mo has high energy s (740 – 780 keV), and contributes to pt dose by 
Al+++ interferes with labeling process, clumps RBCs and can cause microemboli
“Moly breakthrough” test – at first elution
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

39. Impurity limits Test Frequency Limit
Mo Every elution < 0.15 mCi Mo breakthrough: (initial elution per mCi Tc radiation dose by NRC) at tadm
Al Every elution <10 ppm breakthrough: (initial elution at tadm clumping of by NRC) may
RBC and be expressed
micro-emboli as mg/ml)

40. Mo-99 breakthrough limit at elution
Due to the slower decay of Mo-99, the limit at time of elution must be smaller than 0.15 mCi Mo-99 per mCi Tc-99m in order to ensure the limit at time of administration.
E.g. the ratio is mCi Mo-99 per mCi Tc-99m at time of elution increases to hr later.
1 mCi Tc-99m  0.25 mCi 12 hr later
0.042 mCi Mo-99  mCi 12 hr later
0.037/0.25 = < 0.15

41. Ratio of (1) to (2) gives amount of Mo
99mTc QC
Place vial of eluate in Pb container, measure activity. This represents ONLY the Mo activity
Place vial in plastic sleeve, measure activity. This represents BOTH Mo and Tc
Ratio of (1) to (2) gives amount of Mo
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

42. Aluminum ion (Al+++) breakthrough
Al3+ ion is measured colorimetrically. A drop of the eluate is placed on one end of a test paper and a drop of a standard solution of Al3+ with a concentration of 10 ppm is placed on the other end of the test strip. If the color at the center of the drop of eluate is less red than that of the standard solution, the eluate passes the ion breakthrough test.
10 ppm Al3+
standard
generator
eluate

43. 99mTc – a workhorse in NM!
T1/2 = 6 hr – ideally suited to study metabolic processes in patients
140 keV emission - low patient dose & ideal for gamma cameras
No high-energy - radiation – low pt dose
Versatile chemistry - can form tracers by being incorporated into a range of biologically-active substances to target tissue or organ of interest
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

44. Ideal imaging radiopharmaceuticals
Gamma energy keV photons
high enough to escape patient (lowers pt dose) but low enough to be detected (high detection efficiency)
Half life
several minutes to days to allow enough uptake in tissue and fast clearance from blood
High target / background ratio
Limited contamination, e.g. Tc-99m/Mo-99 > %
Chemical properties: easy to attach to a wide range of biochemical compounds
Cost-effective and convenient
Nuclear Medicine Physics for Radiology Residents Sameer Tipnis, PhD, DABR

45. Radionuclides used in nuclear medicine
Less than 20 radionuclides but hundreds of labeled compounds
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps, 4th edition, 2012

46. Selected clinical nuclear medicine procedures
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps, 4th edition, 2012

47. Radiopharmaceutical preparation
Radiopharmaceutical is a compound attached with a radionuclide:
Tc-99m MDP (bone metastasis)
Tc-99m sestamibi (myocardial perfusion)
Or using ionic form e.g. NaI (I--131), TCl (Tl+-201)
It determines the biodistribution  How much radioactivity goes to an organ?
It determines the biological half life  How much radioactivity remains in an organ?
Safety requirements: non-toxic, sterile, and pyrogen-free

48. Tc-99m labeled radiopharmaceuticals
Mix of 99mTcO4_ (pertechnetate) and a cold kit containing a reducing agent (stannous chloride) to lower oxidation states and to bind to a ligand
© Physics in Nuclear Medicine: Cherry, Sorenson and Phelps, 4th edition, 2012