Clinical meeti g

1. RADIOPHARMACY: AN
INTRODUCTION TO ITS CLINICAL
APPLICATIONS
Presenter: Dr. Emejulu Jacinta
Moderator: Dr. Ozolua Nkiru

2. What is RADIOPHARMACY?
 A specialty area of
pharmacy practice
dedicated to the
compounding and
dispensing of
radiopharmaceuticals
for use in nuclear
medicine procedures.

3. What is radiopharmacy (contd)
 COMPOUNDING: FORMULATION OF PHARMACEUTICAL REAGENT
KITS FROM RAW INGREDIENTS FOR THE PREPARATION OF
RADIOPHARMACEUTICALS BY THE ADDITION OF RADIOISOTOPES.
 CRITICAL TO THE IMPLEMENTATION OF AREAS OF NUCLEAR
MEDICINE.
 radiodiagnosis
 pretargeted radioimmunotherapy of cancer
 Molecular imaging
 radioimmunoassay.

4. What is NUCLEAR MEDICINE?
 A specialty of
medicine and medical
imaging that uses
radiopharmaceuticals
in the diagnosis and
treatment of diseases.

5. What is NUCLEAR MEDICINE?
 Nuclear medicine tests differ from most other imaging
modalities in that its diagnostic tests primarily shows the
physiological/functions of the system being investigated
as opposed to traditional anatomical imaging such as CT
or MRI.
 The most intensively used radioisotope is technetium -
99m.
 RADIOTHERAPY: Radiation used to treat cancer

6. NUCLEAR MEDICINE(cont)

7. HISTORY OF NUCLEAR PHARMACY
PRACTICE
 The development of
nuclear pharmacy as a
specialty area
followed the
development of
nuclear medicine as a
recognized specialty
by the American
Medical Association in
the early 1970's.
 in 1970 W.Eckelmen and P.
Richards developed Tc-99m
“instant kit”
radiopharmaceuticals. The
first one was Tc-99m-DTPA.
 In 1896 Henri Becquerel
diccovered mysterious “rays”
from uranium.
 In 1969 C. L. Edwards
reported the accumulation of
gallium-67 in cancer.

8. RADIOPHARMACEUTICALS
 MAY BE A RADIONUCLIDE OR
LABELLED COMPOUND
 STERILE AND NON PYROGENIC
 MINIMAL PHARMACOLOGIC EFFECT.
 PREPARED AS UNIT DOSES
CONTAINING THE RIGHT AMOUNT
OF RADIOACTIVITY PREPARED FOR
INDIVIDUAL PATIENTS.
 95% USED FOR DIAGNOSTIC
PURPOSES USED IN TRACER
QUANTITES
 RADIO PHARMACIES GENERALLY
PRODUCE FROM 2,000 TO OVER
10,000 DOSES EVERY YEAR.
 MUST UNDERGO QUALITY CONTROL
MEASURES REQUIRED OF A
PHARMACEUTICAL .
 SUBJECT TO LICENSING
 PHARMACEUTICAL REGULATIONS
 REGULATIONS GOVERNING
RADIOACTIVE MATERIALS.
 ADDITIONAL REGULATIONS MAY APPLY
FOR ISSUES SUCH AS
TRANSPORTATION OR DISPENSING OF
RADIOPHARMACEUTICALS

10. IDEAL RADIOPHARMACEUTICAL
 PHARMACEUTICAL
 PREFERENTIAL
LOCALISATION IN A GIVEN
ORGAN
 HIGH TARGET TO NON
TARGET ACTIVITY RATIO
 SAFE NON TOXIC FOR
HUMAN ADMINISTRATION
 RADIONUCLIDE
 EMMISSION OF
DETECTABLE RADIATION
 SHORT AND EFFECTIVE
HALF LIFE
 DECAY BY ELECTRON
CAPTURE
 EASY AVAILABILITY

11. Steps for targeted radio nuclei use in cancer
therapy.
 Identification of the biological target on the tumour
exclusively expressed by the tumour.
 A radiopharmaceutical is then designed to target the
tumour expressed biological maker.
 The radio nuclei emit beta and alpha rays capable of
causing DNA damage and leading to death of the
tumour.
 Examination of off-target distribution of the agent.
 Monitoring response to treatment after targeted radio
nuclei therapy.

12. FLOW CHART SHOWING ACTIVITIES OF A
RADIOPHARMACIST

13. What are the clinical applications of
Radiopharmacy ?
Diagnostic
 The radiopharmaceutical
accumulated in an organ of interest
emit gamma radiation which are
used for imaging of the organs with
the help of an external imaging
device called gamma camera.
 They can also be used to predict
the effect of a surgery and assess
changes after treatment.

14. Applications of Radiopharmacy Contd.
Treatment
 radiolabelled molecules are
designed to deliver therapeutic
doses of ionizing radiation to
specific diseased sites.
 They have fewer side effects than
the traditional radiation therapy.
 Traditionally effective to both
isolated tumors and metastatised
tumor.

15. Applications of Radiopharmacy Contd.
 Research
They are administered to track
metabolic reaction and kinetics
including biodistribution, bio
avaliabilityu ete.
They can also be used to study and
detect water resourses and detect
the presence of pollution by use of
harmless radioactive tracers.

16. MAIN RESPONSIBILITIES OF A
RADIOPHARMACIST
 PREPARATION AND
DISPENSING OF
RADIOPHARMACEUTICALS
 QUALITY
CONTROL/QUALITY
ASSURANCE.
 QUALITY AUDITS OF
RADIOPHARMACY SERVICES
 MAINTENANCE AND
MONITORING OF
FACILITIES AND
EQUIPMENT
 IMPROVING COST
EFFECTIVENESS OF
DIAGNOSTIC TESTS
 RESEARCH AND
DEVELOPMENT OF NEW
RADIO-PHARMACEUTICALS,
INCLUDING CLINICAL
TRIALS
 DEVELOPMENT OF NEW
DISPENSING TECHNIQUES
 PROVIDING CLINICAL
INFORMATION ON NEW
PRODUCTS

17. CLINICAL ROLES OF A RADIOPHARMACIST
ADVISING ON
 POSSIBLE CAUSES OF
ABNORMAL
BIODISTRIBUTIONS.
 USE OF MEDICINES THAT
WILL INTERFERE WITH SCAN
QUALITY OR RESULTS.
 STABILITY AND
FORMULATION OF
RADIOPHARMACEUTICALS.
 SPECIAL DOSAGE
FORMULATIONS
 HEALTH AND SAFETY FOR
INDIVIDUALS WHILE USING
RADIOPHARMACEUTICALS
 USE OF
RADIOPHARMACEUTICALS IN
ANIMALS.
 REPORTING ADVERSE DRUG
REACTIONS

18. RADIOPHARMACY STAFF AND TRAINING
 ANATOMY,
 HAEMATOLOGY
 LAW
 COMPUTER SKILLS
 UNDERSTANDING OF
MANDATORY LEGISLATION
AND GUIDANCE.
 NUCLEAR PHYSICS
 RADIATION
PROTECTION
 CHEMISTRY,
 BIOCHEMISTRY,
 RADIOCHEMISTRY,
 IMMUNOLOGY,

19. RADIATION TYPES
 Unstable atoms emit ( give radiations0 from their nuclei . An unstable
nucleus can emit alpha, beta or gamma radiation. Note the properties
of the different rays below.
Alpha
particles
• Stopped by a sheet
of paper.
Beta
particles
• Stopped by a layer
of clothing
• Or by a thin layer of
a substance such as
aluminium.
Gamma
rays
• Has a very high
penetrating power but
can be stopped by a
dense material like
leed.
• Or a few feet of
concrete.
Radiation
source.

20. RADIOISOTOPES USED IN NUCLEAR
MEDICINE
1. ARTIFICIAL
2. PRODUCED FROM
 CYCLOTRON
 NUCLEAR REACTOR
TYPE OF RADIONUCLIDE
DEPENDS ON
 IRRADIATING PARTICLE
 ENERGY
 TARGET NUCLEI

21. PRODUCTION OF RADIONUCLIDES
 CYCLOTRON PRODUCED
 GALLIUM-67
 IODINE123
 INDIUM-111
 CARBON-11
 FLUORINE-18
 OXYGEN-15
 REACTOR PRODUCED
 IODINE-131
 MOLYBDENUM-99
 CHROMIUM-50
 XENIUM-133
 CEASIUM-137

22. Production of radioisotopes
The production of radioisotopes is expensive!
 It is based on four different methods:
• nuclear fission (reactor breeding
• neutron activation processes
• charged particle induced reactions
• radionuclide generator (chemical method)
Each method provides useful isotopes with differing
characteristics for nuclear imaging.

23. CONCEPT OF
RADIONUCLIDE
GENERATORS
 > 90 % of radiopharmaceuticals in
clinical use contain radionuclides
with short half-lives, commercial
supply is often impractical.
 Radiopharmaceuticals which
contain radionuclides with long
half-lives, are obtained from
commercial suppliers
 IMPORTANT RADIONUCLIDE
GENERATORS IN CLINICAL USE
 Moly99-Tc99m generator
 Ge68-Ga68 Generator
SERVE AS CONVENIENT
SOURCES OF
PRODUCTION OF
RADIONUCLIDES ON
SITE IN CLINICAL
RADIOPHARMACY

24. COMPARISM BETWEEN MANUFACTURING AND
COMPOUNDING IN RADIOPHARMACY
MANUFACTURING COMPOUNDING
PRODUCER MANUFACTURER/INDUSTRY HOSPITAL RADIOPHARMACY
SETTING COMMERCIAL CLINICAL
STANDARD GMP CODE OF PRACTICE
REGULATION NATIONAL REGULATORY AUTHORITY PROFESSIONAL
BODIES/INSTITUTION
DISTRIBUTION PUBLIC DISTRIBUTION PRACTITIONER/PATIENT
MARKETING YES NO
PERMISSION INVESTIGATIONAL AUTTHORITY
NEW DRUG APPLICATION
ETHICS COMMITTEE

25. RADIONUCLIDE GENERATORS
 Allows chemical separation of
short-lived radioactive daughter
nuclei with good characteristics
for medical imaging from long-
lived radioactive parent nuclei.
 techniques used are
chromatographic absorption,
distillation or phase separation.
 This method is in particular
applied for the separation of the
rather short-lived 99Tcm (T1/2=6
h) from the long lived 99Mo
(T1/2=2.7 d).
 Applying the radioactive decay law
the growth of activity of the
daughter nuclei A2 with respect of
the initial activity of the mother
nucleus A10 can be expressed in
terms of their respective decay
constants 2 and 2 with 2 >> 1:

26. 99Tcm
 99mTc is used in 80% of NM procedures.
 25 million procedures per annum in the world.
 99Mo/99mTc generators.
 99Mo has half life of 6-7hrs.
 99mTc has a half-life of 6hrs.
 99Tc has a half-life of 211000 hrs.
 99mTc-thyroid cancers
 99mTc-MDP-skeletal
 99mTc-DMSA-kidneys

27. Molybdenum99-Technetium99m generator-
workhorse of nuclear medicine
 the half-life of the mother nuclide
is much longer than that of the
daughter nuclide,
 50% of equilibrium activity is
reached within one daughter half-
life,
 75% within two daughter half-lives.
 removing the daughter nuclide
Tc99m from the generator
("milking" the generator) is
reasonably done every 6 hours or at
most every daughter half life
 commercial Mo-99/Tc-99m
generators use column
chromatography in which Mo-99 is
adsorbed onto alumina.
 Pulling normal saline through the
column of immobilized Mo-99 elutes
the soluble Tc-99m, resulting in a
saline solution containing the Tc-
99m.
 The useful life of a Mo-99/Tc-99m
generator is about 3 half lives or
approximately one week.
 Hence, any clinical nuclear medicine
units purchase at least one such
generator per week or order several
in a staggered fashion.

29. Factors that affect the biodistribution of
radiopharmaceutical.
 Radiopharmaceutical preparation and formulation
problem. E.g the basic shape, size and solubility of
molecule.
 Administration technique and procedure problems.
 Changes in biochemical and pathophysiological e.g
avaliability of compound to tissue, or the proportion of
the tracer that is bound to proteins in the blood.
 Previous medical procedures like surgery or radiation
therapy.
 Drug interactions.

30. COLD KITS
Non-reactive unit dosed reagent kits (cold Unit Doses(cud)) as an efficient and cost
saving method for 99mTc radiopharmaceuticals preparation
 A cold kit contains the
• Ligand to which 99mTc is to be complexed.(organ specific)
• Reducing agent. Sn(II) Chloride
• Buffer to adjust the pH for labelling(NaoH/HCL)
• Stabilising agents(ascorbic acid)
• Excipients for isotonicity(Nacl)
 Stored in a refridgerator at a temperature of 2-8
 Prepared in freeze dried form
 Long shelf life.

36. RADIATION PROTECTION PRINCIPLES
 TIME:
Minimize the amount of time during exposure.
 DISTANCE:
Maximize the distance from the radiation source. The inverse-square law state
that as you double the distance from the radiation source, you reduce the
exposure level by one fouth (1/4th).
 SHIELDING:
Utilize shielding to avoid direct exposure to the radiation source.

37. PRECAUTIONS TO BE TAKEN IN HANDLINGT
RADIOPHARMACEUTICALS.
 The working areas should not get contaminated with radioactive material.
 If the radioactive liquid has to be handled, it must be carried in trays having absorbent
tissue paper so that any spillage will be absorbed by the paper.
 Rubber gloves have to be used when working on the radioactive liquids.
 Pipettes operated by mouth should never be used.
 The radioactive emitter should be handled with forceps and never by hand.
 Sufficient shielding device should be used.
 The radiopharmaceutical materials are stored in suitable labelled containers, shielding
by bricks and preferably in a remote corner.
 Great care has to be applied for disposal of radioactive materials.
 A regular monitoring of radioactivity be done in area where radioactive materials are
stored.

39. CAREER AS A SPECIALIST RADIOPHARMACIST
 Radiopharmacy provides pharmacists with the opportunity to be a keypart of
a multidisciplinary nuclear medicine team. “It is a job where you can use the
science background that is part of your pharmacy degree, as well as giving
you contact with patients, managerial experience and practical work.”
 There is opportunity to go into researching the pathway of many drugs using
imaging techniques.
 The future of cancer treatment is in radiopharmacy-- targeted radionuclide
therapy
 For those pharmacists thinking about a career in radiopharmacy wishing to
follow a career that is intellectually and scientifically challenging, with
opportunity to interact with a wide range of scientists, clinicians and
technologists, then radiopharmacy may be the one.

40. REFERENCES
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and ethics, responsibility, standards of practice and audit. In: Sampson CB. Textbook of
Radiopharmacy. 3rd ed.
3. The Netherlands: Gordon and Breach; 1999. pp271–813. THE RADIOPHARMACY: A
TECHNOLOGISTS GUIDE,EANM PUBLICATION
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5. TOMORROW,S PHARMACIST : A CAREER AS A RADIOPHARMACIST.UKRG PUBLICATION.
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FUNDAMENTALS ON NUCLEAR PHARMACY FIFTH EDITION
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MEDICINE DEPARTMENT
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