Introductory Radiation Biology 2003
Exam I
WHEREVER POSSIBLE, SHOW ALL WORK!!! AND UNITS!!!

1. The microwaves in your oven have an energy of 6.15 * 10 ^-5 eV. What is the frequency and what is wavelength of these photons?

2. ⁶⁴ ₂₉Cu (T _1/2 = 12.7 h) is one of only 62 radionuclides that decay by emission of two certain types of charged particles. In 17.4% of events, Q = 655 keV and ⁶⁴ ₂₉Cu decays to⁶⁴ ₂₈Ni (stable). In 39.0% of events, Q = 573 keV and ⁶⁴ ₂₉Cu decays to ⁶⁴ ₃₀Zn (stable).

1. Sketch a decay scheme that is consistent with this information.
2. The stable isotopes of copper are ⁶³ Cu and ⁶⁵ Cu. Therefore, ⁶⁴ Cu
   1. is proton rich.
   2. is neutron rich.
   3. behaves as if it is both proton rich and neutron rich.
   4. is useless for biological and medical applications.
3. Emission of these two charged particles accounts for 56.4% of ⁶⁴Cu decay events. In the remaining 43.6% of events, ⁶⁴Cu decays by
   1. spontaneous fission.
   2. electron capture.
   3. isomeric transition.
   4. alpha emission.
4. During the decay of ⁶⁴Cu, it emits a 1.35 MeV gamma ray in 0.6% of events and an average of only 2 Auger/conversion electrons. Therefore, the majority of the remaining radiation emitted by ⁶⁴Cu is in the form of
   1. x-rays.
   2. alpha particles.
   3. neutrons.
   4. nuclear recoil.
5. At Washington University in St. Louis, Dr. Carolyn Anderson is evaluating ⁶⁴Cu-TETA-octreotide, a tumor-targeting peptide, for diagnostic imaging of cancer. A cancer patient receives an injected dose of 3 mCi, and 60% of that dose is eliminated in the urine within 4 hours, after which no further excretion occurs. How much ⁶⁴Cu (in mCi) remains in the patient when images are acquired at 6.35 hours post-injection?

3. The half-value layer of the 141 keV ^99mTc gamma ray is 0.27 mm in lead.

1. What is the linear attenuation coefficient (μ) of this photon in lead?
2. How many mm of lead are required to reduce the initial intensity (I₀) of these gamma rays by 99.99% (i.e., I_t = 0.01% of I₀)?
3. Approximately how many half-value layers (HVLs) is this?

4. The range of a 3 MeV electron in soft tissue is 15 mm.

1. What is the LET (in keV/μm) of this electron in soft tissue?
2. Estimate the LET (in keV/μm) of a 3 MeV alpha particle (i.e., ⁴₂He²⁺) in soft tissue.

5. TRUE/FALSE

1. The range of a 1.33 MeV ⁶⁰Co gamma ray is shorter than the range of a 15 MeV LINAC electron in soft tissue. _____
2. Radionuclides produced by charged particle accelerators (e.g., cyclotrons) usually decay by positron emission or electron capture, making them useful for diagnostic imaging._____
3. Beta particles emitted during radioactive decay are always monoenergetic._____
4. Henri Becquerel won the 1901 Nobel Prize in Physics for his discovery of x-rays._____
5. As the energy of a given type of charged particle increases, its linear energy transfer (LET) decreases._____
6. Bremsstrahlung radiation is a type of x-ray that is observed as unique peaks at discrete energies, while “characteristic” x-rays of elements are observed over a continuous energy spectrum._____
7. When a high-energy charged particle (e.g., a 5 MeV alpha particle) collides with an atom in an absorbing medium, it usually transfers most of its kinetic energy to that atom._____
8. Without knowing the source, one can easily distinguish a 250 keV x-ray from a 250 keV gamma ray, using a conventional radiation detector._____

6. Rank the following forms of ionizing radiation in order of increasing range in soft tissue. (Fill in the blanks: rank the least penetrating radiation number 1 and the most penetrating radiation number 6.)

1. 15 MeV electron _____
2. 2.75 MeV gamma ray _____
3. 650 keV positron _____
4. 100 keV x-ray _____
5. 5 MeV proton _____
6. 5 MeV alpha particle _____

7. In terms of radiation biology effects, the most important mechanism by which photons interact with soft tissue is

1. the photoelectric effect.
2. Compton scattering.
3. transfer of an average of 60 eV by collision with an atom.
4. pair production.
5. none of the above.

8. You may have heard the story of the “radioactive Boy Scout,” who got busted by the police while trying to build a breeder reactor in his garage, by extracting large quantities of thorium from Coleman lantern mantles and americium from smoke detectors. (This is a true story!) Suppose he succeeded in building his reactor and it underwent a critical “meltdown,” causing him to absorb a lethal dose of radiation. In all likelihood,

1. he would have glowed in the dark until he succumbed to radiation toxicity.
2. the radiation would have immediately induced spontaneous human combustion.
3. he would have preferred to absorb the same amount of energy by drinking one sip of hot coffee.
4. he would have been posthumously awarded the radiation biology merit badge.

9. If a CT scanner has a tungsten x-ray tube, the range of its 62 keV photon in soft tissue is

1. approximately 15.6 cm.
2. highly variable.
3. finite, but impossible to measure experimentally.
4. infinite.
5. none of the above.

10. Anytime a nucleus is capable of emitting a gamma ray,

1. the gamma ray energy could be imparted to an orbital electron, which is ejected as a conversion electron.
2. it must be undergoing isomeric transition.
3. it must have been left in an excited state following alpha or beta decay.
4. all of the above.
5. none of the above.

11. Briefly define, identify, or describe:

1. Ionizing radiation
2. Radioactive decay
3. LET
4. Name one person who discovered naturally occurring radioactivity
5. Mean free path
6. The predominant decay mode of fission and reactor products
7. Half-life of a radionuclide

INTRODUCTORY RADIATION BIOLOGY
EXAM II, 2003

1. A radiation worker received a whole body dose of 50 mrads from fast neutrons (QF = 20) and a whole body dose of 120 mrads from gamma rays.
   1. Calculate the # mrem the worker received from the 50 mrad dose of fast neutrons.
   2. Calculate the total # mrem this worker received (i.e., from their neutron dose plus the gamma-ray dose
   3. alculate the number of mSv the worker received from 50 mrad fast neutron dose.
      
2. Survival curves A, B and C were obtained as a result of irradiating three different human cell lines with ionizing radiation.

   

   Refer to the above graph in answering the True/False statements below.

   1. ___ From the information in the graph, you would say that Curve C represents a higher radiation sensitivity than Curve B.
   2. ___ Curve A was likely the result of using high LET radiation while Curve C was the result of using Low LET radiation.
   3. ___ Curve B is representative of killing cells primarily by a one hit mechanism.
   4. ___ The D₀ of Curve B is higher than the D₀ of Curve C.
      
3. (a) Describe (using a sketch) creation of a double strand break on a DNA molecule by a one-hit process.
   (b) Describe (using a sketch) how a double strand break on a DNA molecule can be created by a two-hit mechanism.
   (c) The rate at which the radiation dose (dose rate effect) will have a greater effect on the rate of killing of the cells by the one hit process is delivered compared to the rate of cell killing by a two-hit process. (True/False).
   
4. Identify which of the following species/molecules are free radicals.
   1. H₂O
   2. O ₂
   3. H₂O₂
   4. OH
   5. OH^-
   6. H
   7. e^-aq
      
5. Explain “Elkind Repair”. (A sketch of a graph could help)
   
6. a)Explain briefly the “Oxygen Effect”.
   b) Explain why this is an important factor in limiting the ability of Radiation Oncologists to treat tumors in patients with high-energy electron beams or X-rays (a sketch may help).
   
7. Briefly explain or define
   a. Free radical
   b. OER
   c. D₀ and how it mathematically relates to the radiation biologists concept of “sensitivity”.
   d. X-P cells and their relative sensitivity to UV light.
   e. Why a fast neutron will, on the average, lose more of its energy in a single collision with a hydrogen atom nucleus (i.e., a proton) compare to the average amount of energy lost during a single collision with a lead atom nucleus.
   f. Sub-lethal damage
   g. Reproductive death
   h. Why a double strand break of DNA is considered a form of irreparable damage.
   
8. TRUE-FALSE
   a. ___ The RBE generally decreases as LET is increased.
   b. ___ Human lung cells in culture were irradiated with 2 MeV protons. These cells were irradiated under an atmosphere where P_O2=150 mmHg. The OER for these oxygenated cells irradiated with the 2 MeV protons beam is expected to be between 2.5 – 3.0.
   c. ___ In the “linear-quadratic” model, the quadratic term for cell killing decreases (relative to the linear term) as the radiation dose to cells irradiated under O₂ with X-rays as the dose increases in the high dose region (i.e., >300 rads).
   d. ___ The “Base-Excision” repair mechanism is more involved with the repair of damage done to cells by X-rays than is the ‘Nucleotide-Excision” repair mechanism.
   e. ___ Ionizing radiation predominantly causes damage to the bases (i.e., T, C, G, or A) comprising DNA molecules by “excitation” (i.e., promoting an orbital electron to higher energy, excited state molecular orbital).
   f. ___ Glutathione is a molecule containing thiol (-SH) groups. You would expect that the addition of excess glutathione to cell suspensions would sensitize those cells to ionizing radiation when irradiated with X-rays.
   g. ___ You would expect that organisms which only have single stranded DNA will not be able to repair X-ray damage to their DNA as readily as organisms (e.g., human cells) that have double stranded DNA.
   

INTRODUCTORY RADIATION BIOLOGY
FINAL EXAM, 2003

1. A radiation worker received a whole body dose of 5 mrads from fast neutrons (QF=20) and 75 mrads from 1 MeV gamma-rays for the 2003 calendar year.
   1. Calculate the total equivalent dose (in mrem units) this person received in 2003 (show work).
   2. Calculate this person’s dose for 2003 in mSv units.
      
2. Briefly explain the reason that it is not possible to demonstrate a statistically significant increase in the number of lung cancers (i.e., reflecting those that could be attributed to exposure to ionizing radiation) in a population (e.g., an N of 100,000) receiving a radiation dose of 5 rads from a whole body exposure of of 1 MeV gamma-rays.
   
3. List or identify at least four effects that are produced at statistically significant levels as a result of in utero exposure of a human embryo or fetus to a radiation dose of 100 rads from gamma-rays during the first trimester.
   
4. a) According to the UNSCEAR report handout and discussions during class, it is estimated that approximately _______________ cancer deaths will be produced in a population of 1 million people receiving a whole body radiation (low LET) dose of 1 rem each.
   b) Using this risk estimate and assuming a linear, non-threshold relationship, calculate the number of cancer deaths that would be produced by exposure of a group of 10,000 people given 50 rem of whole body low LET radiation each (show work).
   
5. Which two of the following cancer types are NOT one of the four most readily (i.e., cancers produced per rem) produced by ionizing radiation.
   a. lung cancer
   b. thyroid cancer
   c. skin cancer
   d. liver cancer
   e. leukemia
   
6. Briefly define or describe
   a. The general excision repair process
   b. Double strand break
   c. The rem unit
   d. Cell survival curve
   e. linear, non-threshold extrapolation
   f. irreparable DNA damage caused by a one-hit process
   
7. TRUE-FALSE
   ___ a. There are selected populations of humans that have lived for generations in areas of the world where the natural background radiation is elevated (i.e., approximately 500 mrem/year from naturally occurring radioisotopes present in the soil). It has been shown that the cancer rate is significantly higher in these populations when compared to similar populations living in areas where the natural background radiation levels are not elevated.
   ___ b. There are some types of cancers that have been shown to be produced specifically (ONLY) by ionizing radiation. Thus, these radiation-induced cancers do not normally occur in the U.S. population.
   ___ c. The hydroxide anion (i.e., OH ^-) is not a free radical.
   ___ d. A handout provided in class provided mortality data of the Japanese A-bomb Survivor Cohort. It showed that by 1990, there were approximately 8,000 total cancer deaths in this cohort population. An estimate of the number of these cancer deaths in this population that could be attributed to the radiation exposure from the A-bomb was also provided. This estimate indicated that much less than half of the 8,000 cancer deaths were caused by the radiation exposure.
   ___ e. The rate of production (number of effects per rem) of radiation-induced hereditary effects is much higher than the rate of production (number of cancers per rem) of radiation-induced cancers in our population.
   ___ f. Oxygen (O₂) is considered a radiosensitizer.
   ___ g. If the D₀ for human kidney cells is 400 rads and the D₀ for human liver cells is 150 rads, you would consider the liver cells to be more radiation sensitive than the kidneys cells.

Introductory Radioation Biology 32
FINAL EXAM QUESTIONS 2003—Michael R. Lewis, Ph.D.

1. Rank the following ionizing radiations in order of increasing linear energy transfer (LET) (i.e., beginning with the lowest LET; e.g., a < b < c < d, but please note that this may or may not be the correct answer!).
   a.15 MeV electron
   b.5 MeV proton
   c.250 keV x-ray
   d.6 MeV alpha particle
   
2. Molybdenum-99 ( ⁹⁹₄₂Mo; T_1/2 = 66 h) decays to ^99m₄₃Tc (T_1/2 = 6 h), which lies 141 keV above the ground state and decays to ^99g₄₃Tc (T_1/2= 211,100 y). ^99gTc finally decays to ⁹⁹₄₄Ru (stable).
   a. Sketch a decay scheme that is consistent with this information.
   b. ^99mTc decays predominantly by ____________________________________.
   c.True or False (circle one): ^99mTc decay can be imaged efficiently by a conventional gamma camera.
   d. You are a nuclear medicine physician, and unfortunately your ^99mTc generator does not meet Federal guidelines for ⁹⁹Mo contamination. Therefore, you must obtain 25 mCi of ^99mTc-sestamibi, by overnight delivery from Mid-America Isotopes, for a stress test at 9 a.m. on Thursday, December 18. How much ^99mTc-sestamibi (in mCi) does Mid-America Isotopes have to package at 9 a.m. on Wednesday, December 17, in order for your patient to receive the required injected dose?
   
3. Briefly define or describe (no more than 1-2 sentences):
   a. The type of radiation that positron emission tomography (PET) scanners detect
   b. Half-value layer (HVL or X_1/2)
   c. Wilhelm Conrad Röntgen
   d. Ionizing radiation
   e. The predominant process by which photons of energy between 100 keV and 10MeV interact with soft tissue.
   
4. TRUE/FALSE
   _____A 5 MeV alpha particle will have lower LET and cause less biological damage over its track than a 5 MeV β ^- particle.
   _____Radionuclides produced by charged particle accelerators generally decay by electron capture and/or positron emission, making them potentially useful for diagnostic imaging.
   
5. MULTIPLE CHOICE
   1. Na¹³¹I is useful for treatment of
   a. hyperthyroidism (Grave’s disease).
   b. non-Hodgkin’s lymphoma.
   c. differentiated thyroid carcinoma.
   d. final exam-induced anxiety disorder.
   e. both (a) and (c) above.
   
6. I [¹⁸F]Fluorodeoxyglucose (FDG) is taken up readily by tumors, brain, and heart, because these tissues
   a. are interesting to nuclear medicine radiologists.
   b. exhibit high rates of glucose metabolism and “trap” FDG.
   c. express abnormally low levels of glucose transporters.
   d. all of the above.
   e. none of the above.
   
   II. In order to determine whether a patient with skeletal metastases from prostate cancer is a good candidate to use ¹⁵³Sm-EDTMP (QuadraMet™) for pain relief, the appropriate diagnostic test is
   a imaging with ²⁰¹TlCl.
   b. imaging with ¹⁸F-FDG.
   c. imaging with ^99mTc-MDP.
   d. imaging with ^99mTc-DTPA.
   e. the number of jumping jacks the man can do.
   
   III. In the future, many diagnostic and therapeutic radiopharmaceuticals for cancer will be targeted by specific binding to molecules, such as receptors, present on the surface of tumor cells. An example of such a radiopharmaceutical is
   a. Na¹³¹I.
   b. ^99mTc-MAA (Macro-Aggregated Albumin).
   c. ¹⁵³Sm-EDTMP (QuadraMet™).
   d. ¹⁸F-FDG.
   e. ¹¹¹DTPA-octreotide (OctreoScan ®).

Questions – NE 328 Final – Dr. Lattimer
Pick the one best answer for each of the following questions. 5 points each

1. The DNA of the cells is the most sensitive target in the cell for ionizing radiation. Which of the following is the mechanism by which the majority of the injury to the DNA occurs?
   1. a) The radiation interacts directly with the DNA molecule breaking bonds in the base pair lattice.
   2. The radiation interacts directly with the DNA molecule breaking bonds in the sugar-phosphate backbone of the molecule.
   3. The radiation interacts with water in the nucleoplasm, which results in the formation of free oxygen and hydroxyl radicals, which then interact with and damage the DNA.
   4. The radiation interacts which free oxygen atoms in the nucleoplasm, ionizing them and the oxygen radical then interact with and damage the DNA
   5. The radiation interacts directly with the centromere of the chromosomes, which shatters the central portion of the DNA molecule.
2. The outcome of the ionizing radiation injury can be several things. Which of the following results is the most likely to allow the cell to survive?
   1. Apoptosis
   2. Repair
   3. Mitotic Delay
   4. Translocation
   5. Substitution
3. The Cell Cycle is the life cycle of the cell. The end result of a cell passing through the cell cycle is cellular reproduction, which is when the cell is most sensitive to the effects of ionizing radiation. Luckily this part of the cell cycle is relatively short. Which portion of the cell cycle does the cell spend most of its time in?
   1. M phase
   2. S phase
   3. G2 phase
   4. G1 phase
   5. Anaphase
4. Cellular kinetics play an important role in the way in which radiation injury is manifest. Some cells manifest radiation injury quickly and others take a significant period of time to manifest that injury. Which of the following cell types will take the longest to manifest injury when it is in its native tissue.
   1. Vegetative intermitotic cells
   2. Differentiating intermitotic cells
   3. Reverting postmitotic cells
   4. Fixed postmitotic cells
   5. Multipotential connective tissue cells
5. Assays of cells’ ability to reproduce are used to test the ability of a cell type to survive radiation injury and be able to repopulate a tissue. This is referred to as clonogenic potential. Which of the following assays is a procedure where the cells are irradiated in their original location and then after irradiation removed and reinjected into another animal and the number of colonies formed assayed. This can be a model of cancer metastastis.
   1. “in Vitro” clonogenic assay
   2. “in Vivo” clonogenic assay
   3. “in Vivo” transplantation assay
   4. “in Vivo” survival assay
   5. “in Vivo” functional assay
6. The way in which a cell population responds to a radiation injury is in some ways determined by the type of cell, which it is. Which of the following cell types would be most likely to respond to a moderately severe dose (5-6 Grey) of photon radiation by repopulation of the tissue with the same type of cell.
   1. Kidney glomerulus cells
   2. Neurons
   3. Muscle cells
   4. Spermatagonia
   5. Intestinal epithelial cells
7. A fetus’s response to radiation injury differs with the stage of the pregnancy. Which of the following time periods during a human pregnancy is the result of a 2 Grey dose of radiation most likely to be a malforming birth defect, which disfigures the baby physically?
   1. 1 through 2 weeks after conception
   2. 3 through 6 weeks after conception
   3. 7 through 12 weeks after conception
   4. 13 through 24 weeks after conception
   5. 25 through 38 weeks after conception
8. The survival curve for cells following radiation injury is initially a short straight line from the zero dose and 100% survival point which after a relatively modest dose curves downward eventually arriving at a different steeper slope on a long – linear plot. Which of the following mechanisms is generally considered to be responsible for the curved portion of the graph between the initial and second slopes of the survival curve?
   1. Re-oxygenation
   2. Repair
   3. Reassortment
   4. Repopulation
   5. Recuritment
9. The shape of the cell survival curve is somewhat different for different types of cells with cells such as bone marrow cells having a relatively sharp shoulder and cells such as muscle cells having a broader shoulder. Which of the following differences between these two types of cells is thought to be responsible for the difference in the shoulder of the survival curves between these two cell types?
   1. One is an epithelial cell and one is a mesenchymal cell.
   2. One is a short-lived cell and the other is a very long-lived cell.
   3. One is fixed within a tissue matrix and the other is not
   4. One has a very high metabolic rate and the other a low metabolic rate.
   5. One is generally well oxygenated and the other is not.
10. When we do radiation therapy for treatment of cancer it is generally the practice to give many small does of radiation spread out over several weeks rather than one or a few large doses of radiation in a short period of time. Which of the following represents the principal reason for this being done.
    1. It is done to minimize the long-term effects of the radiation on normal tissue.
    2. It is done to maximize the effects of the radiation on the tumor tissue.
    3. It is done to allow normal tissues to repopulate between radiation doses.
    4. It is done to maximize the difference in radiation response between the acute responding cancer tissues and the late responding normal tissues.
    5. It is done to allow normal tissues to reoxygenate between radiation doses.