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Radiopharmaceuticals

Radiopharmaceuticals consist of a radioactive isotope, which creates the image, and a pharmaceutical, which determines the physiological behaviour of the compound and, therefore, where the signal accumulates to form the image.

Radiopharmaceutical
Radiopharmaceutical

There are several properties of the ideal radioisotope for diagnostic purposes (i.e. not therapeutic):

  • Half life which is short enough to limit radiation dose to patient but long enough to allow good signal during imaging (ideally 1.5 x length of imaging)
  • Emits gamma rays which are of high enough energy to leave the body, reach the camera and contribute to the image. The low energy of alpha or beta particles means they are absorbed by the body which increases the radiation dose to the patient and limits the radiation that reaches the camera to produce the image
  • Mono-energetic gamma emitter (i.e. gamma rays of one energy). The ideal energy range is 100 to 250 keV for optimal imaging
  • Decays to stable daughter isotopes that will not cause significant radiation dose to patient
  • Easy to bind to different pharmaceuticals
  • Doesn’t change behaviour of pharmaceutical

And there are several properties of the ideal pharmaceutical:

  • High target:non-target uptake ratio
  • Easy and cheap to produce
  • Non-toxic
  • Does not alter physiology in order to give accurate depiction of patient’s physiology

Clinical radiopharmaceuticals

There are many combinations of radioisotopes and pharmaceuticals that are used in medicine and in imaging. Some of these will produce an image and other will just produce a measurement but no image.

Classification by system

The most common imaging tests for different systems have been outlined below. 

Cardiac imaging

  • Thallium-201: For myocardial perfusion. Injected while the patient is in peak exercise or shortly after the pharmacological stress agent (adenosine) is administered. Patient is imaged immediately to see muscle that is non-perfused and then 3-4 hours later to see muscle that is persistently non-perfused i.e. irreversible infarct vs. poorly perfused i.e. ischaemia.
  • Technetium-99m (99mTc) sestamibi or tetrofosmin: For myocardial perfusion. This has a shorter half-life than thallium-201. It also requires a second injection on the delayed study.
  • MUGA: For ventriculography. The patient’s RBCs are radiolabelled and injected back into the patient. This study is used to assess regional and global wall motion, ventricular function and cardiac chamber size but not myocardial perfusion.

Endocrine imaging

  • 99mTc-pertechnetate: For thyroid function. Patient is imaged within 15-30 minutes after injection. 
  • 99mTc-sestamibi or tetrofosmin: for parathyroid function. Patient scanned at 20 minutes and 2 hours after injection.
  • Iodine-131 MIBG: For neuroendocrine imaging. Thyroid blockade administered 5 days before scan. Patient imaged 1-2 days after injection of I131-MIBG.
  • 99mTc-MDP (methylene diphosphonate): For bone scan. Imaged 2-5 hours after injection. Can be performed as SPECT.

Renal imaging

  • Tc99m-DTPA and Tc99m-MAG3: For GFR estimation. Dynamic images acquired for 25-30 minutes after injection. Can give diuretics.
  • Tc99m-DMSA: For cortical function e.g. scarring. Patient imaged 3 hours after injection. Static study, not functional.

CNS imaging

  • Brain SPECT with technetium-99m HMPOA: Start imaging patient 20 minutes to 2-3 hours after injection.
  • Iodine 123 Ioflupane (aka DaTscan): SPECT. Used in imaging Parkinson’s disease. Thyroid blockade administered. Patient imaged 3-6 hours after injection.

Lung imaging

  • 99mTc-DTPA aerosol: For ventilation. Static image immediately after inhalation.
  • 99mTc-MAA injection: For perfusion. Imaged immediately after injection then static images taken from different angles.

Infection / inflammation imaging

  • Gallium-67 citrate: Performed for regional or whole body imaging, planar or SPECT. Patient imaged at 48 hours and 72 hours.

Oncology imaging

  • Gallium-67 citrate: For non-Hodgkin lymphoma, melanoma and hepatocellular carcinoma. Image on day 2 and 3.
  • 99mTc-octreotide: imaged at 2-4 hours and at 4 hours
  • 18F-FDG PET: Imaged at 30-60 minutes after injection for 5-60 minutes.

GI imaging

  • 99mTc-mebrofenin: For hepatobiliary function. Continuous dynamic imaging up to 60 minutes. Delayed imaging at 3-4 hours if needed.
  • Radiolabeled test meal using 99mTc-sulfur colloid: For gastric emptying. Planar images taken 1 minute immediately after then repeated for 1 minute every hour.

Classification by radioisotope

Below is a summary of each radioisotope and the common uses. In the radioisotope header is the radioisotope, type of radiation emitted, method of production and half-life. For each radiopharmaceutical is the method of administration, whether it is used in vivo or in vitro, clinical use and whether it produces images or not. Despite the length of this table it is not exhaustive!

Carbon-11Positron Cyclotron20.3 m 
C11-CholineIVIn vivoPET: suspected prostate recurrenceImaging
C11-L-Methyl-methionineIVIn vivo

Brain tumour imaging

Parathyroid imaging

Imaging
Carbon-14Beta Reactor5730 y 
C14-Glycocholic acidOralIn vitroBreath test for small intestine bacterial overgrowthNon-imaging
C14-UreaOralIn vitroBreath test for H. pyloriNon-imaging
Chromium-51Gamma Reactor28 d 
Cr51IVIn vitroRBC volume heart scan, RBC sequestration, GI blood lossNon-imaging
Cr51-EDTAIVIn vitroGFRNon-imaging
Cobalt-57Gamma Cyclotron279 d 
Co57-CyanocobalaminOralIn vitroGI absorptionNon-imaging
Fluorine-18Positron Cyclotron109 m 
F18-FDGIVIn vivo

Tumour imaging

Myocardial imaging

Imaging
F18-Sodium fluorideIVIn vivoBone imagingImaging
F18-FluorocholineIVIn vivoProstate cancerImaging
F18-DesmothoxyfallyprideIVIn vivoDopamine receptor imagingImaging
Gallium-67Gamma Cyclotron78.3 h 
Ga67-Ga3+IVIn vivo

Tumour imaging

Infection / inflammation

Imaging
Ga67-CitrateIVIn vivo

Hodgkin’s disease, lymphoma, bronchogenic carcinoma

Acute inflammation

Imaging
Gallium-68PositronGenerator68 m 
Ga68-DotatocIVIn vivoNeuroendocrine tumourImaging
Ga68-PSMAIVIn vivoProstate cancerImaging
Indium-111GammaCyclotron1.81 d 
In111-DTPAIntraperitonealIn vivoVentriculoperitoneal shunt patencyImaging
In111-DTPAIntra-cisternalIn vivoCisternographyImaging
In111-leucocytesIVIn vivoInfection / inflammationImaging
In111-plateletsIVIn vivoThrombus imagingImaging
In111-Pentetreotide or OctreotideIVIn vivoNeuroendocrine tumourImaging
Iodine-123GammaCyclotron13.2 h 
I123-IodideIV or oralIn vivo

Thyroid function

Thyroid cancer metastases

Imaging
I123-MIBGIV In vivoNeuroectodermal tumour imagingImaging
I123-ioflupane aka DaTscanIVIn vivoSPECT: Parkinson’s diseaseImaging
Iodine-131Gamma and betaReactor8.06 d 
I131-IodideOralIn vivoHyperthyroidism / thyroid cancer treatmentTherapeutic
I131-IodideIV or oralIn vivoThyroid metastasesImaging
I131-MIBGIVIn vivoNeuroectodermal tumour imagingImaging
Krypton-81mGammaCyclotron13 s 
K81m-gasInhalationIn vivoLung ventilation imagingImaging
Kr81m-aqueous solutionIVIn vivoLung perfusion imagingImaging
Oxygen-15PositronCyclotron2.04 s 
O15-waterIV bolusIn vivo

Cerebral blood flow

Myocardial blood flow

Imaging
Strontium-89BetaReactor50.5 d 
Sr89-ChlorideIVIn vivoBone metastases treatmentTherapeutic
Technetium-99mGammaGenerator6.02 h 
Tc99m-PertechnetateIVIn vivo

Thyroid uptake and imaging 

Stomach and salivary glands

Meckel’s diverticulum

Brain imaging

Imaging
Tc99m-human albuminIVIn vivo

Cardiac blood pool / peripheral vascular imaging

Lung perfusion imaging

Imaging
Tc99m-Phosphonates and phosphatesIVIn vivo

Bone imaging

Myocardial imaging

Imaging
Tc99m-DTPAIVIn vivo

Renal imaging

Brain imaging

Imaging
Tc99m-DTPAInhalationIn vivoLung ventilationImaging
Tc99m-DMSAIVIn vivo

Tumour imaging

Renal function

Imaging
Tc99m-ColloidIVIn vivo

Bone marrow

GI bleeding

Imaging
Tc99m-ColloidInterstitialIn vivoLymph node drainageImaging
Tc99m-ColloidOralIn vivo

Oesophageal transit and reflux

Gastric emptying

Imaging
Tc99m-HIDAIVIn vivoFunctional biliary systemImaging
Tc99m-denatured RBCsIVIn vivo

RBC volume

Spleen imaging

Imaging
Tc99m-whole RBCsIVIn vivo

GI bleeding

Cardiac blood pool

Imaging
Tc99m-MAG3IVIn vivoRenal imagingImaging
Tc99m-HMPOAIVIn vivoCerebral blood flowImaging
Tc99m-examatazime labelled leucocytesIVIn vivoInfection / inflammationImaging
Tc99m-SestamibiIVIn vivo

Parathyroid / thyroid

Myocardial

Imaging
Tc99m-TetrosfosminIVIn vivo

Parathyroid

Myocardial

Imaging
Tc99m-TilmanoceptInterstitial Lymphatic mapping with handheld gamma counterNon-imaging
Thallium-201GammaCyclotron73.5 h 
Tl201-Tl+IVIn vivo

Thyroid tumour / parathyroid adenoma

Myocardial

Imaging
Xenon-133GammaReactor2.26 d 
Xe133-gasInhalationIn vivoLung ventilationImaging
Xe133 in isotonic sodium chloride solutionIVIn vivoCerebral blood flowImaging

Written by radiologists, for radiologists with plenty of easy-to-follow diagrams to explain complicated concepts. An excellent resource for radiology physics revision.

Next page: Gamma camera

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