Radiopharmaceuticals (EXAM 3)

Question 1

What are the types of radiation?

Answer 1

-unstable (protons and neutrons are unbalanced) elements trying to get stability back

-by Radiation: Alpha, Beta, Gamma

Question 2

Which particles are emitted by different types of radiation?

Answer 2

-Alpha: 2 protons and 2 neutrons (positively charged)
-Beta: electrons (negatively charged)
-Gamma: non-particles, electromagnetic photon (waves)
-> Gamma radiation can be detected -> used in Imaging

Question 3

Ionizing Radiation

Answer 3

the more ionizing, the less able to penetrate bc the energy is transferred readily
Alpha (++): poor penetration, gets absorbed easily -> used for smoke detectors, evaluate prostate and bone cancer)

Beta (-): moderate penetration, radiation therapy

Gamma: no charge -> good penetration, for diagnostics

Neutron: no charge, very penetrative

Question 4

Unit of Radioactivity

Answer 4

-Curie (Ci)
-disintegration per second (dps)
-SI unit is Bacquerel

Question 5

How is the radioactivity that reaches the body measured?

Answer 5

-Rad or Radiation Absorbed dose = ergs = energy absorbed by 1g of tissue
-SI unit = 1 gray = 100 rad

Question 6

How is the shelf-life of radioactive material measured?

Answer 6

-By the half-life
-Radioactive decay follows first-order kinetics -
-constant time needed to half the amount is constant bc the rate is proportional to the amount
(in zero order the time needed will change)

Question 7

How are radioactive materials produced (Radioisotopes)?

Answer 7

-bombarding it with neutrons in cyclotrons -> creates unstable atoms -> Radioisotopes
-they are unstable and have short half-life

Question 8

Thyroid and Renal Imaging

Answer 8

-With Iodine(131) -> the thyroid produces T3, T4 (3 or 4 iodines attached) -> the thyroid gland uses iodine, so it easily taken up radioactive Iodine (uptake pumps) -> the more active the gland is the more it will take iodine and the clearer the image will be

-Kidney: in vivo Benzylalcohol is metabolized by conjugation with glycin to Benzyl-glycin = hippuric acid (neonates cant conjugate benzyl alcohol)
-> I-131-ortho-iodohippuric acid is secreted by 100% by the kidney, displaying the function of the kidney of transplant patients

Question 9

How is cardiac function evaluated?

Answer 9

-with Thalium 201
-when the heart is beating fast the cardiac artery is dilated for blood supply
-NORMAL: both at rest and stress -> image with blood supply

-ISCHEMIA: defect on stress, but fills on redistribution

-INFARCT: defect on both, bc the tissues is infarcted and died out - no blood supply

Question 10

Pulmonary Imaging

Answer 10

-with Technitium (99mTc, gamma emission)
-imaging to check the function of lungs, the more it takes it up the clearer -> non-functional can be treated with stenting and checked again for proper Technitium uptake

Question 11

Bone scans

Answer 11

-with Technitium-99m -> metastable for shorter half-life -> you want the material to get out of the body ASAP
-short half-life (6h)
-imaging bone, heart, thyroid, brain, and other organs
-to localize the cancer

Question 12

Helicobacter Pylori imaging

Answer 12

-H. pylori uses enzymes to form a buffering shield of ammonia to survive at low pH in the stomach

-C-14 capsules with urea dissolve in the stomach, and when H. pylori is present it uses ureases to convert urea to ammonium and C-14 bicarbonate -> which is exhaled as C-14 CO2 -> measurable

Question 13

Positron Emission Tomography (PET scanning)

Answer 13

-Positrons are equivalents to an electron but (+) charged
-when colliding with electrons of tissues, they emit gamma radiation -> detected by gamma-ray cameras

-imaging metabolically active tissues like brain and cancer-> F-18 (gamma-emitter) labeled glucose

Question 14

What is the difference between PET and CT scans?

Answer 14

CT scan: multiple X-ray scans stacked together: a static picture

PET-scan: dynamic or functional image to identify metabolically active areas

Question 15

How is imaging helpful in Drug discovery/development?

Answer 15

-quantitative whole-body autoradiography is performed after dosing with a radiolabeled drug that is studied -> to see where the drug goes (toxicity)
-study of drug elimination

Question 16

How is radiation used for imaging different from the usage in treatment?

Answer 16

Dosing
-Hyperthyroidism (Grave’s) or thyroid cancer or multinodular goiter -> intend to kill, 5-10k larger dose

• Strontium chloride (~50-day half-life) and 153 Samarium EDTMP (~50 h half-life) -> note the half-life, certain half-life is necessary to kill, too much is also not preferred

Question 17

How can radioactivity be used in cancer treatment?

Answer 17

-prostate-specific membrane antigen expressed by cancerous cancer cells
-radioisotope lutetium-177 tagged to a prostate antigen-specific antibody (tagged to Fc part)
-beta and gamma radiation

Question 18

Why is ß radiation better than gamma radiation in cancer treatment?

Answer 18

-ß Radiation is charged, making it more powerful
-uncharged radiation is preferred in imaging than in cancer therapy

(alpha radiation is more powerful but hard to work with)

Question 19

Drugs used with radiolabeled mAb

Answer 19

-Trastuzumab (Herceptin) targets HER2 receptors on breast cancer cells
-Lutetium (t1/2, 6.7 days) delivers beta and gamma radiation to the HER2 breast cancer cells

Question 20

What are important protection practices?

Answer 20

Time (exposed to radiation), distance, shielding

Question 21

What is the material of the shielding barriers?

Answer 21

Leaded glass stops radiation, but can’t block neutrons
Neutrons can only be blocked by Concrete

Question 22

How are radioactive drugs compounded?

Answer 22

Comes in a kit (without radionuclide) -> reconstituted
-quality control testing
-activity measured in milliCuries
-often solution and injection
-often Technitium 99 used as a radionuclide

Question 23

Extension of BUDs

Answer 23

-Package insert suggest use-by time
-products must be labeled
Radiopharmacists are eligible to extend BUDs if analytical studies support compliance with USP specifications