Rubidium-82 (⁸²Rb) is a

radioactive Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is conside ...

isotope Isotopes are distinct nuclear species (or ''nuclides'') of the same chemical element. They have the same atomic number (number of protons in their Atomic nucleus, nuclei) and position in the periodic table (and hence belong to the same chemica ...

rubidium Rubidium is a chemical element; it has Symbol (chemistry), symbol Rb and atomic number 37. It is a very soft, whitish-grey solid in the alkali metal group, similar to potassium and caesium. Rubidium is the first alkali metal in the group to have ...

. ⁸²Rb is widely used in

myocardial perfusion imaging Myocardial perfusion imaging or scanning (also referred to as MPI or MPS) is a nuclear medicine procedure that illustrates the function of the heart muscle (myocardium). It evaluates many heart conditions, such as coronary artery disease (CAD), ...

. This isotope undergoes rapid uptake by myocardiocytes, which makes it a valuable tool for identifying myocardial

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems ...

Positron Emission Tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

(PET) imaging. ⁸²Rb is used in the pharmaceutical industry and is marketed as Rubidium-82 chloride under the trade names RUBY-FILL and CardioGen-82.

History

In 1953, it was discovered that rubidium carried a biological activity that was comparable to

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

. In 1959, preclinical trials showed in dogs that myocardial uptake of this radionuclide was directly proportional to myocardial blood flow. In 1979, Yano et al. compared several ion-exchange columns to be used in an automated ⁸²Sr/⁸²Rb generator for clinical testing. Around 1980, pre-clinical trials began using ⁸²Rb in PET. In 1982, Selwyn et al. examined the relation between myocardial perfusion and rubidium-82 uptake during acute ischemia in six dogs after coronary stenosis and in five volunteers and five patients with

coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...

. Myocardial tomograms, recorded at rest and after exercise in the volunteers showed homogeneous uptake in reproducible and repeatable scans. Rubidium-82 has shown considerable accuracy, comparable to that of ^99m Tc-

SPECT Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...

. In 1989, the FDA approved the ⁸²Rb/⁸²Sr generator for commercial use in the U.S. With increased ⁸²Sr production capabilities, the use of ⁸²Rb has increased over the last 10 years and is now approved by several health authorities worldwide.

Production

Rubidium-82 is produced by

electron capture Electron capture (K-electron capture, also K-capture, or L-electron capture, L-capture) is a process in which the proton-rich nucleus of an electrically neutral atom absorbs an inner atomic electron, usually from the K or L electron shells. Th ...

of its parent nucleus, strontium-82. The generator contains accelerator-produced ⁸²Sr adsorbed on stannic oxide in a lead-shielded column and provides a means for obtaining sterile nonpyrogenic solutions of

rubidium chloride Rubidium chloride is the chemical compound with the formula RbCl. This alkali metal halide salt is composed of rubidium and chlorine, and finds diverse uses ranging from electrochemistry to molecular biology. Structure In its gas phase, RbCl is d ...

(halide salt form capable of injection). The amount (millicuries) of ⁸²Rb obtained in each elution will depend on the potency of the generator. When eluted at a rate of 50 mL/minute, each generator eluate at the end of elution should not contain more than 0.02 microcuries of strontium ⁸²Sr and not more than 0.2 microcuries of ⁸⁵Sr per millicurie of ⁸²RbCl injection, and not more than 1 microgram of tin per mL of eluate.

Pharmacology

Mechanism of action

⁸²Rb has activity very similar to that of a potassium ion (K⁺). Once in the

myocardium Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...

, it is an active participant in the sodium-potassium exchange pump of cells. It is rapidly extracted by the myocardium proportional to blood flow. Its radioactivity is increased in viable myocardial cells reflecting cellular retention, while the tracer is cleared rapidly from necrotic or infarcted tissue.

Pharmacodynamics

When tested clinically, ⁸²Rb is seen in the myocardium within the first minute of intravenous injection. When the myocardium is affected with ischemia or infarction, they will be visualized between 2–7 minutes. These affected areas will be shown as photon deficient on the PET scan. ⁸²Rb passes through the entire body on the first pass of circulation and has visible uptake in organs such as the kidney, liver, spleen and lung. This is due to the high vascularity of those organs.

Use in PET

Rubidium is rapidly extracted from the blood and is taken up by the myocardium in relation to myocardial perfusion, which requires energy for myocardial uptake through Na⁺/K⁺-ATPase similar to thallium-201. ⁸²Rb is capable of producing a clear perfusion image similar to single photon emission computed tomography(SPECT)-MPI because it is an extractable tracer. The short half-life requires rapid image acquisition shortly after tracer administration, which reduces total study time. The short half-life also allows for less radiation experienced by the patient. A standard visual perfusion imaging assessment is based on defining regional uptake relative to the maximum uptake in the myocardium. Importantly, ⁸²Rb PET also seems to provide prognostic value in patients who are obese and whose diagnosis remains uncertain after SPECT-MPI. ⁸²Rb myocardial blood flow quantification is expected to improve the detection of multivessel coronary heart disease. ⁸²Rb/PET is a valuable tool in

identification. Myocardial Ischemia is an inadequate blood supply to the heart. ⁸²Rb/PET can be used to quantify the myocardial flow reserve in the ventricles which then allows the medical professional to make an accurate diagnosis and prognosis of the patient. Various vasoreactivity studies are made possible through ⁸²Rb/PET imaging due to its quantification of myocardial blood flow. It is possible to quantify stress in patients under the same reasoning. Recently it has been shown that neuroendocrine tumor metastasis can be imaged with ⁸²Rb due to its ability to quantify myocardial blood flow (MBF) during rest and pharmacological stress, commonly performed with adenosine.

Advantages

One of the main advantages of ⁸²Rb is its availability in

nuclear medicine Nuclear medicine (nuclear radiology, nucleology), is a medical specialty involving the application of radioactivity, radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, ''radiology done inside out'', ...

departments. This isotope is available after 10-minute

elution In analytical and organic chemistry, elution is the process of extracting one material from another by washing with a solvent: washing of loaded ion-exchange resins to remove captured ions, or eluting proteins or other biopolymers from an el ...

of a ⁸²Sr column; this makes it possible to produce enough samples to inject about 10–15 patients a day. Another advantage of ⁸²Rb would be its high count density in myocardial tissue. ⁸²Rb/PET has shown greater uniformity and count density than ^99mTc-SPECT when examining the myocardium. This results in higher interpretive confidence and greater accuracy. It allows for quantification of coronary flow reserve and myocardial blood flow. ⁸²Rb also has an advantage in that it has a very short half-life which results in much lower radiation exposure for the patient. This is especially important as the use of myocardial imaging increases in the medical field. When it comes to patients, ⁸²Rb is beneficial to use when the patient is obese or physically unable to perform a stress test. It also has side effects limited to minor irritation around the injection site.

Limitations

A serious limitation of ⁸²Rb would be its cost. Currently ^99mTc costs on average $70 per dose, needing two doses; whereas ⁸²Rb costs about $250 a dose. Another limitation of this isotope is that it needs a dedicated PET/CT camera, and in places like Europe where a ⁸²Sr/⁸²Rb generator is still yet to be approved that can be hard to find.