NM 4103

Radiopharmaceuticals &Quality Control

What is a Radiopharmaceutical?• Radionuclide

– Allows imaging

• Pharmaceutical– Chosen based on localization

Ideal Radiopharmaceutical

• Easily produced

• Inexpensive

• Readily available

• Short half-life

• Gamma rays

Half-Life

• Physical– Time for radionuclide to reduce activity by

one-half

• Biologic– Excretion, perspiration

• Effective– Physical and biologic half-lives

Common Radionuclides

99mTc - Technetium 6 hours123I – Iodine 13.2 hours131I - Iodine 8 days133Xe - Xenon 5.3 days67Ga - Gallium 78.3 hours111In - Indium 67 hours201Tl – Thallium 73.1 hours

How do they do that?

• 99mTc eluted from generator Mix Kits Images

• Physiology Methods of localization

Methods of LocalizationPassive Diffusion

• Compound diffuses across a biologic membrane from a

compartment of higher concentration to one of lower concentration.

• 99mTc-DTPA (brain imaging)• 99mTc DTPA aerosol• 133Xe ventilation• 111In DTPA cisternography• Myocardial perfusion with 99mTc Sestamibi • Filtration of 99mTc DTPA by kidney

Methods of localizationIon Exchange (Chemisorption)• The diophosphates are absorbed onto and

form a complex with the Calcium Hydroxyapatite crystals. They bind exclusively to the mineral phase of the bone and not to organic matrix.

• Phosphate bone-scanning (MDP, HDP)• Where bone modeling is most active is

where the highest amount of Tc-MDP accumulates.

Methods of localizationCapillary blockage

• Pulmonary capillaries and small arterioles trap larger

particles

• 99mTc MAA particles trapped in the lung capillaries

Methods of localizationPhagocytosis• Engulfment and ingestion by specialized cells

– Colloid scanning for Liver (middle range particles) – Colloid scanning for the Spleen (largest particles)– Colloid scanning for bone marrow (smallest particles)– Colloid scanning for lymph nodes

• Removal of 99mTc sulfur colloid particles by the reticuloendothelial cells in the liver, spleen and bone marrow

Methods of localizationActive Transport• Movement of a compound across a biologic

membrane against a concentration gradient, uphill, from a lower to a higher concentration.– Iodine or Tc for thyroid– Pertechnetate for Meckel’s diverticulum– Pertechnetate for stomach– Pertechnetate for choroid plexus– Pertechnetate for hepatobiliary imaging– Pertechnetate for salivary gland– Thallium in myocardium

Methods of localizationCell Sequestration• To separate certain cells apart from the

whole

• Leukocytes for abscess scanning (WBC)• Labeled platelets• Sequestration of heat-damaged 99mTc

labeled rbc’s by the spleen

Methods of localizationMetabolism• 18F-FDG uptake in myocardial, brain

tissues and tumors

• PET imaging ~ glucose metabolism

Methods of localizationReceptor binding• 11C-dopamine binding to the dopamine

receptors in the brain ~ Neuroreceptor imaging

Methods of localizationCompartmental localization• Partitioning and Retention of the

radiopharmaceutical into a biologic compartment.– Cardiac scanning with labeled RBC’s

(gated blood pool)– Cisternogram with In111 DTPA (injected

intrathecally and confined to CSF

Compartmental Leakage : Labeled RBC’s for GI

bleeding detection

Methods of localizationAntigen-antibody • Specific for a tumor associated antigen

imaging

• Localizes via an antibody-antigen reaction

• Monoclonal antibodies

• 131 I , 111In and 99mTc labeled antibody to localize tumors

Methods of localizationChemotaxis• 111In labeled leukocytes to localize

infections

Biodistribution• Consists of absorption, distribution, metabolism,

plasma clearance and excretion.• Organ systems involved in 99mTc pertechnetate

biodistribution:*Stomach* Salivary glands* Thyroid* Bowel* Choroid plexus* Brain* Sweat glands* Kidney

Reducing agent

• Chemically, 99mTcO-4 is nonreactive

and won’t label by direct addition of a pharmaceutical compound.

• The oxidation state needs to first be reduced to allow reaction (tagging)

• Reducing agents:– Stannous chloride (most common)– Stannous citrate, stannous tartrate,

ferrous sulfate, sodium borohydride

Oxygen in the vial

• Oxygen can cause oxidation of the stannous ion– Especially before the addition of 99mTc

• Free 99mTc

• Some kits (MDP,HDP) have an antioxidant to prevent oxidation– Ascorbic acid, gentisic acid

Kits

• Facilitated nuclear pharmacy

• Long shelf-life

• Some are as simple as just adding 99mTcO-

4

• Sterile environment, laminar flow hood,

Colloids

• Size falls between a solution and a suspension

• Particles range between 10 nm and 1µm

• Gelatin : stabilizing agent used to prevent aggregation

• Examples : 99mTc Sulfur colloid & 99mTc MAA

Physicochemical Tests

• Determine purity and integrity of a radiopharmaceutical– Check for particulate matter, color, clarity– Particle size /number of colloids checked under

microscope

• pH : 2-9 (ideal is 7.4 ~ same as blood)• Radionuclide Purity : Moly breakthrough• Radiochemical Purity : free 99mTcO-4• Chemical Purity: Aluminum

Biologic Tests

• Sterilization: membrane filtration is most common– Radionuclides can be sensitive to heat

sterilization– Sterility testing takes longer than the half-

life of radionuclides.

Nuclear Pharmacy

• Lab coat

• Gloves

• Tongs

• Lead barrier shield

• Laminar flow hood

• Aseptic technique

Dispensing

• Prescription

• Name

• ID number

• Technologist

• Type of radiopharmaceutical

• Dose given

Pediatric doses

• Biodistribution is different in children

• Dose must be adjusted

• Usually calculated based on weight or body surface area

Disposal

• Decay in storage ~ most common

• Sewer

• Incineration

• Burial in landfill

Decay in Storage

• Radionuclides with half-lives of 120days or less.

• Can be released to waste when:– 10 half-lives– Radioactivity cannot be detected above

background– Radioactive signs are removed

Sewerage system

• Radioactive material must be soluble

• Biologic matter

• Quantity of monthy allowances

Transfer to an Authorized Recipient• Long-lived radionuclides

• Usually buried or incinerated

Good Practice

• Radiation signs• Wear Lab coat and gloves• Absorbent paper• Lead containers• Film badge• Identify radionuclide containers• Survey work area • Do not eat or drink in radiation lab• Monitor hands and feet