Radiopharmacology

Radiopharmacology is the study and preparation of radiopharmaceuticals, which are radioactive pharmaceuticals. Radiopharmaceuticals are used in the field of nuclear medicine as tracers in the diagnosis and treatment of many diseases. Many radiopharmaceuticals use technetium-99m (Tc-99m) which has many useful properties as a gamma-emitting tracer nuclide. In the book Technetium a total of 31 different radiopharmaceuticals based on Tc-99m are listed for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood and tumors.

The term radioisotope has historically been used to refer to all radiopharmaceuticals, and this usage remains common. Technically, however, many radiopharmaceuticals incorporate a radioactive tracer atom into a larger pharmaceutically-active molecule, which is localized in the body, after which the radionuclide tracer atom allows it to be easily detected with a gamma camera or similar gamma imaging device. An example is fludeoxyglucose in which fluorine-18 is incorporated into deoxyglucose. Some radioisotopes (for example gallium-67, gallium-68, and radioiodine) are used directly as soluble ionic salts, without further modification. This use relies on the chemical and biological properties of the radioisotope itself, to localize it within the body.

Lead container for iodine-123 capsule

History

See nuclear medicine.

Production

Production of a radiopharmaceutical involves two processes:

• The production of the radionuclide on which the pharmaceutical is based.

• The preparation and packaging of the complete radiopharmaceutical.

Radionuclides used in radiopharmaceuticals are mostly radioactive isotopes of elements with atomic numbers less than that of bismuth, that is, they are radioactive isotopes of elements that also have one or more stable isotopes. These may be roughly divided into two classes:

• Those with excess neutrons in the nucleus to those required for stability are known as proton-deficient, and tend to be most easily produced in a nuclear reactor, the majority of radiopharmaceuticals are based on proton deficient isotopes, with technetium-99m being the most commonly used medical isotope, and therefore nuclear reactors are the prime source of medical radioisotopes.

• Those with fewer neutrons in the nucleus to those required for stability are known as neutron-deficient, and tend to be most easily produced using a proton accelerator such as a medical cyclotron.

Practical use

Because radiopharmeuticals require special licenses and handling techniques, they are often kept in local centers for medical radioisotope storage, often known as radiopharmacies. A radiopharmacist may dispense them from there, to local centers where they are handled at the practical medicine facility.

Specific radiopharmaceuticals

A list of nuclear medicine radiopharmaceuticals follows. Some radioisotopes* are used in ionic or inert form without attachment to a pharmaceutical, these are also included. There is a section for each radioisotope with a table of radiopharmaceuticals using that radioisotope. The sections are ordered alphabetically by the English name of the radioisotope. Sections for the same element are then ordered by atomic mass number.

Calcium-47

⁴⁷Ca is a beta and gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Ca-47-Ca2+	Bone metabolism	IV	In-vitro	Non-imaging

Carbon-11

¹¹C is a positron emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
C11-L-methyl-methionine	Brain tumour imaging Parathyroid imaging	IV	In-vivo	Imaging

Carbon-14

¹⁴C is a beta emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
C14-Glycocholic acid	Breath test for small intestine bacterial overgrowth	Oral	In-vitro	Non-imaging
C14-PABA (para-amino benzoic acid)	Pancreatic studies	Oral	In-vitro	Non-imaging
C14-Urea	Breath test to detect Helicobacter pylori	Oral	In-vitro	Non-imaging
C14-d-xylose	Breath test for small intestine bacterial overgrowth	Oral	In-vitro	Non-imaging

Chromium-51

⁵¹Cr is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Cr51-Red blood cells	Red cell volume; sites of sequestration; gastrointestinal blood loss	IV	In-vitro	Non-imaging
Cr51-Cr3+	Gastrointestinal protein loss	IV	In-vitro	Non-imaging
Cr51-EDTA (ethylenediaminetetraacetic acid)	Glomerular filtration rate measurement	IV	In-vitro	Non-imaging

Cobalt-57

⁵⁷Co is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Co57-Cyanocobalamin (vitamin B12)	Gastrointestinal absorption	Oral	In-vitro	Non-imaging

Cobalt-58

⁵⁸Co is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Co58-Cyanocobalamin (vitamin B12)	Gastrointestinal absorption	Oral	In-vitro	Non-imaging

Erbium-169

¹⁶⁹Er is a beta emitter.

Name	Treatment of	Route of administration
Er169-Colloid	Arthritic conditions	Intra-articular

Fluorine-18

¹⁸F is a positron emitter with a half life of 109 minutes. It is produced in medical cyclotrons, usually from oxygen-18, and then chemically attached to a pharmaceutical. See PET scan.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
F18-FDG (Fluorodeoxyglucose)	Tumor imaging Myocardial imaging	IV	In-vivo	Imaging
F18-Sodium Fluoride	Bone imaging	IV	In-vivo	Imaging
F18-Fluorocholine	Prostate tumor imaging	IV	In-vivo	Imaging

Gallium-67

⁶⁷Ga is a gamma emitter. See gallium scan.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Ga67-Ga3+	Tumor imaging	IV	In-vivo	Imaging
Ga67-Ga3+	Infection/inflammation imaging	IV	In-vivo	Imaging

Gallium-68

⁶⁸Ga is a positron emitter, with a 68 minute half life, produced by elution from germanium-68 in a gallium-68 generator. See also positron emission tomography.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Ga68-Dotatoc or Dotatate	Neuroendocrine tumor imaging	IV	In-vivo	Imaging

Hydrogen-3

³H or tritium is a beta emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
H3-water	Total body water	Oral or IV	In-vitro	Non-imaging

Indium-111

¹¹¹In is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
In111-DTPA (diethylenetriaminepenta-acetic acid)	Ventriculo-peritoneal shunt (LaVeen Shunt)	intraperitoneal injection	In-vivo	Imaging
In111-DTPA (diethylenetriaminepenta-acetic acid)	Cisternography	Intra-cisternal	In-vivo	Imaging
In111-Leukocytes	Infection/inflammation imaging	IV	In-vivo	Imaging
In111-Platelets	Thrombus imaging	IV	In-vivo	Imaging
In111-Pentetreotide	Somatostatin receptor imaging	IV	In-vivo	Imaging
In111-Octreotide	Somatostatin receptor imaging (Octreoscan)	IV	In-vivo	Imaging

Iodine-123

¹²³I is a gamma emitter. It is used only diagnostically, as its radiation is penetrating and short-lived.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
I123-Iodide	Thyroid uptake	Oral or IV	In-vivo	Non-imaging
I123-Iodide	Thyroid imaging Thyroid metastases imaging	Oral or IV	In-vivo	Imaging
I123-o-Iodohippurate	Renal imaging	IV	In-vivo	Imaging
I123-MIBG (m-iodobenzylguanidine)	Neuroectodermal tumour imaging	IV	In-vivo	Imaging
I123-FP-CIT	SPECT imaging of Parkinson's Disease	IV	In-vivo	Imaging

Iodine-125

¹²⁵I is a gamma emitter with a long half-life of 59.4 days (the longest of all radioiodines used in medicine). Iodine-123 is preferred for imaging, so I-125 is used diagnostically only when the test requires a longer period to prepare the radiopharmaceutical and trace it, such as a fibrinogen scan to diagnose clotting. I-125's gamma radiation is of medium penetration, making it more useful as a therapeutic isotope for brachytherapy implant of radioisotope capsules for local treatment of cancers.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
I125-fibrinogen	Clot imaging	IV	In-vivo	Imaging

Iodine-131

¹³¹I is a beta and gamma emitter. It is used both to destroy thyroid and thyroid cancer tissues (via beta radiation, which is short-range), and also other neuroendocrine tissues when used in MIBG. It can also be seen by a gamma camera, and can serve as a diagnostic imaging tracer, when treatment is also being attempted at the same time. However iodine-123 is usually preferred when only imaging is desired.

Diagnostic

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
I131-Iodide	Thyroid uptake	Oral	In-vivo	Non-imaging
I131-Iodide	Thyroid metastases imaging	Oral or IV	In-vivo	Imaging
I131-MIBG (m-iodobenzylguanidine)	Neuroectodermal tumor imaging	IV	In-vivo	Imaging

Therapeutic

Name	Treatment of	Route of administration
I131-Iodide	Thyrotoxicosis	IV or Oral
I131-Iodide	Non-toxic goiter	IV or Oral
I131-Iodide	Thyroid carcinoma	IV or Oral
I131-MIBG (m-iodobenzylguanidine)	Malignant disease	IV

Iron-59

⁵⁹Fe is a beta and gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Fe59-Fe2+ or Fe3+	Iron metabolism	IV	In-vitro	Non-imaging

Krypton-81m

⁸¹Kr^m is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Kr81m-Gas	Lung ventilation imaging	Inhalation	In-vivo	Imaging
Kr-81m-Aqueous solution	Lung perfusion imaging	IV	In-vivo	Imaging

Nitrogen-13

¹³N is a positron emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
N13-Ammonia	Myocardial blood flow imaging	IV	In-vivo	Imaging

Oxygen-15

¹⁵O is a positron emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
O15-Water	Cerebral blood flow imaging Myocardial blood flow imaging	IV bolus	In-vivo	Imaging

Phosphorus-32

³²P is a beta emitter.

Name	Treatment of	Route of administration
P32-Phosphate	Polycythemia and related disorders	IV or Oral

Rubidium-82

⁸²Rb is a positron and gamma emitter.

Name	Treatment of	Route of administration
Rb-82 Chloride	Myocardial Imaging	IV

Samarium-153

¹⁵³Sm is a beta and gamma emitter.

Name	Treatment of	Route of administration
Sm153-EDTMP (Ethylenediaminotetramethylenephosphoric acid)	Bone metastases	IV

Selenium-75

⁷⁵Se is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Se75-Selenorcholesterol	Adrenal gland imaging	IV	In-vivo	Imaging
Se75-SeHCAT (23-Seleno-25-homo-tauro-cholate)	Bile salt absorption	Oral	In-vivo	Imaging

Sodium-22

²²Na is a positron and gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Na22-Na+	Electrolyte studies	Oral or IV	In-vitro	Non-imaging

Sodium-24

²⁴Na is a beta and gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Na24-Na+	Electrolyte studies	Oral or IV	In-vitro	Non-imaging

Strontium-89

⁸⁹Sr is a beta emitter.

Name	Treatment of	Route of administration
Sr89-Chloride	Bone metastases	IV

Technetium-99m

⁹⁹Tc is a gamma emitter. It is obtained on-site at the imaging center as the soluble pertechnetate which is eluted from a technetium-99m generator, and then either used directly as this soluble salt, or else used to synthesize a number of technetium-99m-based radiopharmaceuticals.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Tc99m-pertechnetate	Thyroid uptake and thyroid imaging Stomach and salivary gland imaging Meckel's diverticulum imaging Brain imaging Micturating cystogram First pass blood flow imaging First pass peripheral vascular imaging	IV	In-vivo	Imaging
Tc99m-pertechnetate	Lacrimal imaging	Eye drops	In-vivo	Imaging
Tc99m-Human albumin	Cardiac blood pool imaging	IV	In-vivo	Imaging
Tc99m-Human albumin	Peripheral vascular imaging	IV	In-vivo	Imaging
Tc99m-Human albumin macroaggregates or microspheres	Lung perfusion imaging	IV	In-vivo	Imaging
Tc99m-Human albumin macroaggregates or microspheres	Lung perfusion imaging with venography	IV	In-vivo	Imaging
Tc99m-Phosphonates and phosphates	Bone imaging	IV	In-vivo	Imaging
Tc99m-Phosphonates and phosphates	Myocardial imaging	IV	In-vivo	Imaging
Tc99m-DTPA (diethylenetriaminepenta-acetic acid)	Renal imaging First pass blood flow studies Brain imaging	IV	In-vivo	Imaging
Tc99m-DTPA (diethylenetriaminepenta-acetic acid)	Lung ventilation imaging	Aerosol inhalation	In-vivo	Imaging
Tc99m-DMSA(V) (dimercaptosuccinic acid)	Tumor imaging	IV	In-vivo	Imaging
Tc99m-DMSA(III) (dimercaptosuccinic acid)	Renal imaging	IV	In-vivo	Imaging
Tc99m-Colloid	Bone marrow imaging GI Bleeding	IV	In-vivo	Imaging
Tc99m-Colloid	Lymph node imaging	Interstitial	In-vivo	Imaging
Tc99m-Colloid	Esophageal transit and reflux imaging Gastric emptying imaging	Oral	In-vivo	Imaging
Tc99m-Colloid	Lacrimal imaging	Eye drops	In-vivo	Imaging
Tc99m-HIDA (Hepatic iminodiacetic acid)	Functional biliary system imaging	IV	In-vivo	Imaging
Tc99m-Denatured red bood cells	Red cell volume	IV	In-vitro	Non-imaging
Tc99m-Red blood cells	GI bleeding Cardiac blood pool imaging Peripheral vascular imaging	IV	In-vivo	Imaging
Tc99m-MAG3 (mercaptoacetyltriglycine)	Renal imaging First pass blood flow imaging	IV	In-vivo	Imaging
Tc99m-Exametazime	Cerebral blood flow imaging	IV	In-vivo	Imaging
Tc99m-Exametazime labelled leucocytes	Infection/inflammation imaging	IV	In-vivo	Imaging
Tc99m-Sestamibi (MIBI - methoxy isobutyl isonitrile)	Parathyroid imaging Non-specific tumor imaging Thyroid tumor imaging Breast imaging Myocardial imaging	IV	In-vivo	Imaging
Tc99m-Sulesomab (IMMU-MN3 murine Fab'-SH antigranulocyte monoclonal antibody fragments)	Infection/inflammation imaging	IV	In-vivo	Imaging
Tc99m-Technegas	Lung ventilation imaging	Inhalation	In-vivo	Imaging
Tc99m-Human immunoglobulin	Infection/inflammation imaging	IV	In-vivo	Imaging
Tc99m-Tetrofosmin	Parathyroid imaging Myocardial imaging	IV	In-vivo	Imaging
Tc99m-ECD (ethyl cysteinate dimer)	Brain imaging-----	IV	In-vivo	Imaging

...

Thallium-201

²⁰¹Tl is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Tl201-Tl+	Non-specific tumor imaging Thyroid tumor imaging Myocardial imaging Parathyroid imaging	IV	In-vivo	Imaging

Xenon-133

¹³³Xe is a gamma emitter.

Name	Investigation	Route of administration	In-vitro / in-vivo	Imaging / non-imaging
Xe133-gas	Lung ventilation studies	Inhalation	In-vivo	Imaging
Xe133 in isotonic sodium chloride solution	Cerebral blood flow	IV	In-vivo	Imaging

Yttrium-90

⁹⁰Y is a beta emitter.

Name	Treatment of	Route of administration
Y90-Silicate	Arthritic conditions	Intra-articular
Y90-Silicate	Malignant disease	Intracavitary

See also

• Radioactive tracer
• Nuclear medicine

Reading

• Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. Administration of radioactive substances advisory committee. March 2006. Produced by the Health Protection Agency.
• Malabsorption. In: The Merck Manual of Geriatrics, chapter 111.
• Leukoscan summary of product characteristics (Tc99m-Sulesomab).
• Schwochau, Klaus. Technetium. Wiley-VCH (2000). ISBN 3-527-29496-1

External links

• National Isotope Development Center U.S. Government resources for isotopes - production, distribution, and information
• Isotope Development & Production for Research and Applications (IDPRA) U.S. Department of Energy program sponsoring isotope production and production research and development