Peculiarities of

radiopharmaceuticals

Judith Wagener

Scientist: Radiochemistry

2018 PSSA Conference

22-24 June 2018, Birchwood Hotel & OR Tambo Conference Centre, Boksburg

Interesting facts

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Radiopharmaceutical is…….

+

Radiation emitted must be easily detected by nuclear instruments

Allows for in vivo tracking

Radionuclide with emitting radiation that

is measurable

Determines organ specificity

Allows for uptake of radioactivity Must be safe and non-toxic for

human administration

Biological compound/ligand with high uptake into the

target organ

“Making the body biochemically transparent“

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Radiopharmaceutical classification

Diagnostic = imaging Therapeutic = treatment

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Radiation in context

is sterile and pyrogen free

consists of a radionuclide with optimal properties, e.g. γ-emitter with

γ-energies between 100-250 keV for SPECT

can be easily produced, is inexpensive and readily available

should have a relatively short effective half life (balancing act)

ligand/tracer with properties that allow for specific organ targetting

significant/measurable accumulation in target organ

no pharmacological or toxic effect

Ideal diagnostic Radiopharmaceuticals

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Molecular Imaging

-rays travel from within body to outside and can then be detected and imaged

Not a static scan as for a CT- or ‘CAT-scan’

• Mostly intravenously injected

• Small chemical amounts (nanogram)

• Localises in a specific organ via a metabolic process which is then imaged at that time point or

over a time period.

• Functional information in addition to anatomy

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Radiochemistry behind radiopharmaceuticals

Radionuclide production

• Nuclear reactor

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The original 99mTc generator without shielding

Pre/post regulation aspects

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Half life of radioisotopes

Activity decreases with time therefore radioactive concentration

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Less chemical more radio

FDG mass signal undetectable

37 GBq 18F

105.8 ng 18F-FDG

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QC release timeline

• Radiochemical purity

• Chemical purity

• pH

• Bacterial endotoxins

• Filter integrity

• Half-life

• Visual inspection

Release of product for

administration before

confirmation of all

QC-tests

•Radionuclidic purity

•Residual solvents

•Sterility

production Dispatch release Pre-administration

release Post release

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Facility layout

Buffer area (1)

Production

BS

C

En

tran

ce

are

a

Equipment

airlock

RA Plenum

PSH

FC

counter

Hot ce

ll

counter

co

un

ter

Buffer area (2)

Change room

-25kPa

+25kPa

+15kPa

+10kPa

Internal PPE

External PPE

Personnel flow

Material flow

Air flow

Equipment/ instrument flow

ISO 5/6: PEC sterile area

ISO 6/7: Buffer area

ISO 7/8: Ante area

CNC 13

Radiopharma Pharma

Clinical application Therapeutic +Diagnostic Therapeutic (pharmacologic)

Facility HVAC incl pharma + radiological requirement

Negative pressure cascade

HVAC

Positive pressure cascade

Lead shielding No shielding

Legislation SAHPRA (GMP) + Radiation safety regulation SAHPRA (GMP)

Production Small scale Large scale

Limiting shelf-life (hours to days)

Half-life dependant

Longer shelf life (days to years)

Stability of pharmaceutical

QC Physicochemical,

radionuclidic + radiochemical purity

sterility testing

Pre- and post-release testing

Physicochemical

purity

sterility testing

Pre-release testing

Packaging Licensed packaging according to “Russian-doll”

concept – impact product and environment

Approved primary and secondary

packaging - impact to the product

RSP (Radio)pharmacists / QP Radiochemist with

post graduate course in radiopharmaceuticals

– clinicial trials

Pharmacist

Radiopharma vs Pharma

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Take-home wisdom M

arie C

urie

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www.necsa.co.za

Questions?

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