Pharmaceutics Lecture On Nuclear Pharmacy

Front 1

what is nuclear pharmacy?

Back 1

-first specialty in pharmacy recognized in
1978 by the Board of Pharmaceutical
Specialties
-focuses on the safe and effective use of
radioactive drugs
-has become highly specialized and
contributed positively to the practice of nuclear medicine

Front 2

what is radiation?

Back 2

Radiation is energy traveling through space or material in the form of waves or particles
-- atoms
-- stable
-- unstable

Front 3

three types of radiation decay

Back 3

– ALPHA
– BETA
– GAMMA

Front 4

why is the type of emission important?

Back 4

Type of emission that is given off will determine whether or not the
radionuclide will be useful for imaging or treating a patient

Front 5

what is tagging?

Back 5

“Tagging” the radioactive source to some compound that is known to
localize in a specific area of the body, the compound will carry the
radioactive material to the desired site

Front 6

why do you use a specific detection device?

Back 6

By using a specific detection device it is possible to detect the
emissions given off by the radioactive material and create images of
the relative distribution of the radioactive source in the body

Front 7

what is physical half life?

Back 7

-time required for ½ atoms to transform

Front 8

what is biological half life?

Back 8

-time required for ½ material to clear body

Front 9

what is effective half life?

Back 9

-combines atomic and biological for clearance
post intake

Front 10

Decay equation

** It represents every aspect of radiation decay law

Back 10

A(f) = A(i) x e (-kt)

A (f) = Final activity
A (I) = Initial activity
K = ln (2)/ t1/2 = .693 / t1/2
A(f) = A(i) x (decay constant)

Front 11

Ideal Diagnostic Radiopharmaceutical

Back 11

Easy to produce and distribute
• Short effective Half-Life
• Gamma or x-rays
• No pharmacologic action
• Minimal disposal problems
• High yield in photon emission of about 150 kev
• Units of measurement Curie>mCi>uCi

Front 12

radiopharmaceuticals
how many products available?

Back 12

more than 100

Front 13

radiopharmaceuticals
two components:

Back 13

drug and radioactive components

Front 14

radiopharmaceuticals

There is a vital distinction between radioactive and
traditional drugs

Back 14

true

Front 15

radiopharmaceuticals
what percent are labeled with Tc-99m (technetium)

Back 15

80%

Front 16

radiopharmaceuticals
what percent are diagnostic

Back 16

90%

Front 17

radiopharmaceuticals
routes of administration

Back 17

Intravenous, inhalation, oral

Front 18

radiopharmaceuticals
uses:

Back 18

– Asses physiologic function
– Evaluate patient response to drug therapy and surgery
– Helps monitor drug therapy and toxicity
– Treatment of disease
– Stage disease

Front 19

radiopharmaceuticals
two major areas- Diagnostic

Back 19

• Diagnostic –Well established
– Largest applications in cardiology, oncology, neurology
– Infection imaging and nephrology

Front 20

radiopharmaceuticals
two major areas- Therapeutic

Back 20

• Therapeutic – Evolving
– Thyroid Cancer, Graves Dx, Hyperthyroidism, Bone Pain Palliation

Front 21

radiopharmaceuticals and their uses
Diagnostic agents for cancer

Back 21

Tl201-Cl
Tc99m Sestamibi

Front 22

radiopharmaceuticals and their uses
Diagnostic agents for bone

Back 22

Tc99m-Medronate

Front 23

radiopharmaceuticals and their uses
diagnostic agents for inflammation

Back 23

Ga67 Citrate

Front 24

radiopharmaceuticals and their uses
diagnostic agents for Liver &
Lymphoscintgraphy

Back 24

• Tc99m-Sulfur Colloid

Front 25

radiopharmaceuticals and their uses
diagnostic agents for lung

Back 25

Tc99m-Macroaggregated Albumin
Xe133

Front 26

radiopharmaceuticals and their uses
diagnostic agents for Neuroendocrine Tumors

Back 26

In111-Pentetreotide

Front 27

radiopharmaceuticals and their uses
diagnostic agents for brain and tumor

Back 27

F18-FDG

Front 28

radiopharmaceuticals and their uses
therapeutic agents for Thyroid function Hyperthyroid, & Thyroid Cancer

Back 28

Na-I131

Front 29

radiopharmaceuticals and their uses
therapeutic agents for pain palliation of bone metastases

Back 29

Sm153

Front 30

radiopharmaceuticals and their uses
therapeutic agents for non-hodgkin's lymphoma

Back 30

Y90-Ibritumomab Tiuxetan

Front 31

Tc-99m Sulfur Colloid
Lymphoscintigraphy

Back 31

see slide 12 and 13

Front 32

Technetium-99m

Back 32

– Gamma emitter w/o hazardous effects of beta particles
– Flexible chemistry profile
– Used as a radiolabel for various compounds
• Compartmental localization
– Tc-99m RBC in MUGA studies
6 hour t 1/2

Front 33

Thallous-201 Chloride (Tl-201)

Back 33

– Available as a sterile, nonpyrogenic solution for
intravenous administration
– Half life - 73.1 hours
– Undergoes rapid active transport into the myocardium
– Visualizes myocardial infarction and ischemic Heart Dx
– Undergoes fast redistribution; No uptake>infarct

Front 34

Gallium-67 (Ga-67)

Back 34

– Available as a sterile, pyrogen-free aqueous solution
– Half life – 78 hours
– Localizes in primary and metastatic tumors & focal sites of
infection
• E.g.. Sarcoidosis, abscesses and pyelonephritis
– Aids in the diagnosis and monitoring of Pneumocystis Carinii
of AIDS and Fever Of Unknown Origin.
– Ferric Ion increases Ga-67 renal excretion

Front 35

Indium-111 Chloride

Back 35

– Popular for label of MABs
• Antigen-antibody complex formation
– Arcitumomab (CEA-SCAN)
– Satumomab pendetide (Oncoscint)
– Capromab penditide (ProstaScint)
– Long half life
– Lacks beta emission

Front 36

therapeutic radiopharmaceuticals
Strontium-89 Chloride (Metastron)

Back 36

– Sterile, non pyrogenic aqueous solution for intravenous
use; no preservatives
– Beta emitter; Half Life of 51 days
– Very harmful to skeletal tissue
– Used for Bone pain Palliation associated with tumors
and metastasis
– Caution w/ patients of platelet counts below 60,000 and
WBC counts below 2400

Front 37

Therapeutic radiopharmaceuticals
Samarium-153 (Sm-153)

Back 37

– Short half life – 46.3 hours (1.9 days)
– Difficult in manufacturing and delivery
– Low energy beta emitter
– Dose = 1 mCi/kg administered intravenously over 1
minute
– Toxicity
• Limited to bone marrow suppression manifested by
decreased leukocyte counts and thrombocytopenia
• Nadir =4 weeks; Recovery = Normal levels in 6 weeks

Front 38

Therapeutic radiopharmaceuticals
Yttrium-90 (Y-90)

Back 38

– Trivalent radioactive metal
– Half Life – 64.2 hours = 2.68 days
– Sterile, pyrogen free
– Therapeutic application in solid large tumors and
lymphomas

Front 39

monoclonal antibody imaging
In-111 or Y-90

Back 39

– Ibritumomab Tiuxetan, ZEVALIN
• First FDA approved radio immunotherapy agent
• Intended for the treatment of patients with relapsed or
refractory low-grade, follicular b-cell non-Hodgkin’s
lymphoma
• In-111 label: Biodistribution step
• Y-90 label: Therapeutic step
• Very involved process with oncology, nuclear medicine and
radio pharmacy

Front 40

therapeutic radiopharmaceuticals
Sodium Iodide-131 (I-131)

Back 40

– Volatile solution
– Oral capsule or solution
– Localization
• Active Transport
– Small amounts – uCi or 2-5mCi
• Used for thyroid function tests or thyroid uptake tests
– Large amounts – 5-200mCi
• Used for carcinoma, masses, ablation

Front 41

role of radioiodine in thyroid disease

Back 41

see slide 23

Front 42

Localization
passive diffusion

Back 42

– Xe-133, Tc-99m DTPA, In-111 DTPA

Front 43

localization
ion exchange and transport

Back 43

– MDP uptake in bone, Tc-99m thyroid trapping

Front 44

localization
capillary blockade

Back 44

– MAA in lung

Front 45

localization
phagocytosis

Back 45

– SC removal by RES

Front 46

localization
cell sequestration

Back 46

– Removal of denatured RBC by spleen

Front 47

localization
metabolism

Back 47

– F-18 FDG uptake in the heart or brain

Front 48

localization
receptor binding

Back 48

– Somatostatin analogue binding to soft tissue tumors
– Apcitide binding to activated platelets

Front 49

imaging procedures
dynamic

Back 49

Provides useful information through the
rate of accumulation and removal of the
radiopharmaceutical from a specific organ

Front 50

imaging procedures
static

Back 50

Provides perfusion and morphologic
information, such as assessing adequacy of blood
flow; organ size, shape and position; lesions

Front 51

diagnostic imaging

Back 51

Some radiopharmaceuticals are formulated to
be placed within a target organ e.g.. I-131 Dx
• Some radiopharmaceuticals are useful to
evaluate a patient’s response to drug therapy
and surgery e.g.. Tc-99m MAA
• Some radiopharmaceuticals also find utility to
help monitor drug therapy, including drug
toxicity e.g.. Tc-99m MUGA

Front 52

Non Radioactive Pharmaceutical Use
in Nuclear Medicine
dipyridamole (persantine)

Back 52

– Vasodilator, longer t1/2 15-30min, increased side effects

Front 53

Non Radioactive Pharmaceutical Use
in Nuclear Medicine
Adenosine (Adenocard)

Back 53

– Vasodilator, ultra short t1/2 <10secs,

Front 54

Non Radioactive Pharmaceutical Use
in Nuclear Medicine
Aminophylline

Back 54

Reverses effects of the above drugs to relieve side
effects

Front 55

Non Radioactive Pharmaceutical Use
in Nuclear Medicine
Shilling's test

Back 55

– Determines patients ability to absorb Vitamin B12

Front 56

Positron Emission Tomography (PET)

Back 56

– PET Camera
– Exposure rates are 6 x greater
– PET Imaging Drugs
• Rb-82 Rubidium Chloride
• F-18 FDG Fluorodeoxyglucose – 110 min
• F-18 Dopa
• O-15 Water – 2min
• N-13 Ammonia – 10 min

Front 57

• Imaging applications of PET

Back 57

– Mapping regional blood flow and volume
– Oxygen metabolism
– Receptor density
– Cell proliferation
– Tumor receptor density
– Receptor gene expression

Front 58

• FDG-18; Flurodeoxyglucose
half life

Back 58

110 minute

Front 59

• FDG-18; Flurodeoxyglucose
useful in diagnosis of various cancers

Back 59

» Lung, colorectal, melanoma, lymphoma, head and neck

Front 60

• FDG-18; Flurodeoxyglucose
most widely used because:

Back 60

» Useful in tracing glucose metabolism
» Useful in detecting malignant tissue
» Useful in quantifying changes in tumor glycolysis during and
after treatment

Front 61

• FDG-18; Flurodeoxyglucose
uses have expanded

Back 61

» Cerebral – maps normal brain metabolic activity
» Myocardial – identifies regions in which glucose metabolism
increases
» Tumor – Glucose metabolism increases in tumor tissue

Front 62

F-18 FDG Fluorodeoxyglucose

Back 62

• Radio labeled glucose molecule
• Shows metabolism
– Therefore able to image
• Epilepsy
• Cancers
• Altered metabolism relative to normal tissue
• Can show disease before structural changes can be picked
up

Front 63

white blood cell labeling

Back 63

Label white blood
cells with radioactive
drug that is lipophillic
– It enters and gets
trapped in the cell
• WBC’s are
suspended in 3 ml of
plasma. It is reinjected back into the patient
• Follows strict
needless procedure
• Accurate patient ID