Extravasation events in nuclear medicine are rarely fully characterized—including accurate dosimetry and appropriate clinical follow-up. Accurate dosimetry should include the determination of infiltrated fraction of administered activity, clearance half-times, and resulting radiation doses to infiltrated tissue and overlaying skin.
With patient radiation safety in mind, we maintain that both diagnostic and therapeutic extravasation events should be identified and characterized. Severe extravasations affect the diagnostic or therapeutic quality of nuclear medicine procedures, and the unintended dose to tissue and skin may eventually be clinically significant. A dedicated radiopharmaceutical injection monitoring system can be used to improve the accuracy of dosimetry and assist in determining the need for patient follow-up.
Dosimetry
The benefits of nuclear medicine procedures far outweigh the radiation risk when radiopharmaceuticals are properly administered. However, when extravasation occurs, it is important to characterize the absorbed radiation dose to the patient’s tissue and skin. Dosimetry is the process used to perform this characterization. It combines the type of radiation, the amount of radioactivity, and the time that it is present to calculate the amount of energy absorbed by tissue. The amount of absorbed energy correlates with dose to the tissue, and high levels of absorbed dose can lead to adverse tissue reactions and increased chance of carcinogenesis.
Absorbed Dose Calculation Examples
Within the first 1 second following an extravasation, for every millicurie of extravasated isotope there will be 37,000,000 radioactive disintegrations within the tissue surrounding the injection site. During each subsequent second, as the isotope decays, disperses, or is reabsorbed by the lymphatic system, there will be fewer disintegrations. Each of these disintegrations contributes absorbed dose to the surrounding tissue–depending on the emitted decay energy, the isotope-specific half-life, and the rate at which radioactivity leaves the injection-site tissue. The following examples of two of the most commonly used radiopharmaceuticals provide insight into how an extravasation can lead to a high tissue absorbed dose for two hypothetical extravasation scenarios.
Consider an injection of 10 mCi 18F-FDG, of which 5 mCi is extravasated into 5 cm3 to tissue.
18F decays through positron emission (96.86%) which then leads to the 511 keV gamma photons used for PET imaging. The remaining 3.14% of decays undergo electron capture to produce Auger electrons and X Rays, however, their energy emissions are insignificant.
5 mCi =
185,000,000 Bq
185,000,000 * 96.86% =
179,191,000 positrons
Assuming an effective half-life of 45 minutes (physical decay, dispersion, and reabsorption), the total number of positrons emitted within the extravasated tissue is:
179,191,000 positrons * 2,700 seconds / ln(2) =
697,998,511,094 positrons
On average, each emitted positron will have 249.5 keV of energy. Because the maximum range for 18F positrons is a few millimeters, all this energy is assumed to be deposited within the 5 cm3 of tissue surrounding the extravasation.
697,998,511,094 positrons * 249.5 keV =
174,150,628,518,000 keV
Absorbed dose is defined as deposited energy divided by mass, which, for SI units, is J/kg. One Gy of absorbed dose is equal to 1 J/kg. Using an approximate tissue density of 1 g/cm3, a 5 cm3 volume of tissue would have a mass of 5 g, or 0.005 kg.
174,150,628,518,000 keV =
0.028 J
The absorbed dose for a 5 mCi extravasation of 18F-FDG in 5 cm3 is:
0.028 J/0.005 kg =
5.6 Gy
Consider an injection of 25 mCi 99mTc-MDP, of which 15 mCi is extravasated into 5 cm3 to tissue.
Eighty-nine percent of 99mTc decays are through emission of gamma photons with 141 keV of energy. It is these gammas that are used in nuclear medicine imaging. However, 99mTc is not a pure gamma emitter; the remaining 11% of decays are through internal conversion which results in electron emissions.
15 mCi =
555,000,000 Bq
555,000,000 Bq * 11% =
61,050,000 electrons
Along with the relatively longer physical half-life of 99mTc (6 hours), the chemical properties of MDP can limit its rate of biological clearance resulting in a longer effective half-life. Assuming an effective half-life of 240 minutes (physical decay, dispersion, and reabsorption), the total number of disintegrations within the extravasated tissue is:
61,050,000 electrons * 14,400 seconds / ln(2) =
1,268,302,064,000 electrons
The electrons emitted during internal conversion contain approximately 119 keV of energy. Because electron emissions deposit energy locally like beta radiation, all this energy is assumed to be deposited within the 5 cm3 of tissue surrounding the extravasation.
1,268,302,064,000 electrons * 119 keV =
150,927,945,647,000 keV
Absorbed dose is defined as deposited energy divided by mass, which, for SI units, is J/kg. One Gy of absorbed dose is equal to 1 J/kg. Using an approximate tissue density of 1 g/cm3, a 5 cm3 volume of tissue would have a mass of 5 g, or 0.005 kg.
150,927,945,647,000 keV =
0.024 J
The absorbed dose for a 15 mCi extravasation of 99mTc-MDP in 5 cm3 is:
0.024 J/0.005 kg =
4.8 Gy
Historically extravasation dosimetry was dependent on assumptions about the amount and clearance of radioactivity at the administration site. Methods would assume the entire administered activity was extravasated and that there was no biological clearance.* These assumptions result in an overestimation of absorbed dose to tissue because most extravasations do not involve the entire injected activity, and biological clearance will decrease the time that extravasated radioactivity is present within the tissue. To estimate absorbed dose accurately, information is needed about both the amount of radioactivity that was initially extravasated and the rate of biological clearance.
*Dosimetric consequences of interstitial extravasation following i.v. administration of a radiopharmaceutical. Shapiro, B., et al. Eur J Nucl Med: 1987, 12(10): 522-523.
Using static images of the extravasation and dynamic information from the Lara System, estimates of both the initial amount of extravasation and its rate of clearance can be made.**
**Patient-specific Extravasation Dosimetry Using Uptake Probe Measurements. Dustin Osborne, et al. Health Physics: March 2021 – Volume 120 – Issue 3 – p 339-343
The Lara System can help clinicians more accurately characterize extravasations
Health Physics