Questions and Answers

What is an extravasation?
An extravasation is the inadvertent administration of radiopharmaceutical anywhere outside the vascular compartment, such as into the subcutaneous tissue surrounding a vein.
How does extravasation happen?
Some of the injected dose can escape outside the venous compartment as a result of multiple causes.

While gaining access:
• A puncture through the posterior wall of the vein can occur.
• Arm movement, after catheter placement and prior to administration, can cause the catheter tip to damage the vein wall.

During administration:
• Injecting a radiopharmaceutical too rapidly can increase intraluminal pressure enough to rupture the vein wall, sometimes referred to as “blowing a vein”.
• Thrombosis or restriction of the normal venous blood flow, proximal to the administration site, can adversely impede the flow of the radiopharmaceutical to the systemic circulation.

All of these problems are more common in patients with chronic illnesses that have required repeated venous access. Patients with cancer who have been treated with sclerosing chemotherapy regimens are particularly prone to issues with venous access and extravasations.
Does an extravasation unintentionally irradiate arm tissue with radiation?
Absolutely. Excess radiopharmaceutical left near the injection side irradiates the tissue more than if the radiopharmaceutical remains in the vascular system and enters the tissue based on the metabolic need. The degree of irradiation depends on many factors.
What level of unintentional tissue irradiation should concern a patient?
There is no sure answer to this question; however, in the 2001 publication, Guide for Diagnostic Nuclear Medicine, the authors state that adverse tissue reaction effects “occur only after relatively high dose levels that exceed the threshold for those effects, usually a dose on the order of 100 rem (1 Sv).” The Guide for Diagnostic Nuclear Medicine was a collaborative effort by volunteer professionals in the nuclear medicine sciences in cooperation with the staffs of the Society of Nuclear Medicine (SNM) and the Nuclear Regulatory Commission (NRC). The Guide was reviewed by the SNM Board of Directors, the American College of Nuclear Physicians (ACNP) Board of Regents, the Members of the ACNP/SNM Government Relations Committee, and members and staff of the American College of Radiology. NRC staff provided additional information.
There are many examples in the literature of how therapeutic radiopharmaceutical extravasations have resulted in harm to the patient. Can a diagnostic extravasation also cause harm to patients?
Yes. Unlike the many published examples of therapy extravasations, there are only three examples in the literature of patients with diagnostic extravasations having dosimetry performed. All three patients had doses that exceeded 1.0 Sv to their tissue. All three patients were followed for several years. All three had adverse tissue reactions approximately 2 years after the extravasation.
Has Lucerno ever seen diagnostic extravasations that exceeded the threshold noted by nuclear leaders that can lead to adverse tissue reaction effects?
Yes. Lucerno has performed dosimetry on more than 36 significant diagnostic extravasations. Nearly all of them have exceeded the 1.0 Sv threshold and all of them have exceeded the 0.5 Sv NRC medical event reporting limit. Most of these examples have been shared with the NRC.
How long after an extravasation does it take for the biological effects to impact a patient’s tissue?
A recent article by Jaschke et al. suggests it can take months or years for the effects of radiation on tissue to become evident to the patient.
Extravasations can irradiate patient tissue with high doses, but do extravasations really matter to the results of a PET/CT image?
Absolutely. An extravasation can have a major impact on both quantitative and qualitative PET/CT results.
How does an extravasation impact quantitative PET/CT results?
Patients receive a prescribed dose of an 18F-FDG (FDG), which is critical in calculating standardized uptake values (SUVs). When the dose is not completely delivered to the circulation, the SUV calculation and tumor uptake are impacted, leading to incorrect values. Clinicians use SUVs taken before and after treatment in order to assess patient response to therapy. SUVs are also sometimes used to help determine tumor malignancy. Extravasations invalidate quantitative PET/CT results.
How does an extravasation impact qualitative PET/CT results?
The prescribed dose and the length of FDG uptake time are necessary to provide optimal image quality for that patient. When the dose is not completely delivered, tumor uptake is lowered. Additionally, each nuclear medicine center prescribes the amount of time that the FDG should be circulating in the patient’s vascular system to provide them with the optimal results. During ideal administrations, FDG enters the venous system as a bolus and is almost immediately available to the tumor for uptake, leaving small amounts of FDG circulating in the vascular system later in the uptake period. An extravasated dose may leak back into the vascular system during the uptake period and during image acquisition. Since extravasations cause lower tumor uptake and higher FDG levels in circulation during imaging, the tumor-to-background contrast can be reduced, making it more difficult to detect tumors with relatively low metabolic rates. Thus, an extravasation results in degraded PET/CT images used by clinicians to stage and assess therapy.
Is it possible to assess extravasations in PET/CT images and then correct the results?
In current practice the administration site is often not in the image field of view, so not all infiltrations are seen. When an extravasation is in the field of view, it is difficult to accurately quantify using the image. Most importantly, even if one is able to see and quantify the extravasation in a static image, this information may not reflect the true extent of the extravasation at the time of the administration and during the entire uptake period.
Why aren’t administration sites in the field of view all the time? Is this a problem?
During a PET/CT procedure, the most common practice is to have patients place their arms over their heads and to set the field of view from skull base to mid thighs. In this field of view, the administration site is often not visible to clinicians. If an administration site is not in the field of view and there is an extravasation, clinicians using the PET/CT results will be unaware that the image and SUVs are compromised. Other diagnostic nuclear medicine procedures and many therapy procedures also do not include the administration site in the imaging field of view due to the nature of the procedure.
If a clinician can see the administration site, why is it difficult to quantify the extravasation?
It is theoretically possible to quantify how much radiotracer is near the administration site if a trained professional is willing to trace its entire area on every axial slice of the image where an extravasation is visible. But adjustments to the net injected dose that are made by creating a volume of interest that is properly corrected for attenuation, scatter, and partial volume effects is not only labor intensive, it also requires special skills and tools that are not ordinarily deployed in clinical practice. In the end, all of the effort may be of limited value anyway.
Why would quantifying a visible extravasation be of limited value?
The amount of radiopharmaceutical present at the time of image capture (usually 60-90 minutes after the administration for PET/CT, and in many cases longer for SPECT) may not be representative of the amount of radiopharmaceutical that was at the extravasated administration site during the uptake period. In nearly every extravasation case that Lucerno has observed, the radiopharmaceutical at the administration site resolves, either through the body’s lymphatic system or by leaking back into the venous system. As a result, measuring a static image of an extravasation many minutes or hours after it occurs cannot adequately characterize the true nature and extent of the extravasation.
What if the extravasation is truly minor, does that matter to the dose and to the image or therapy results?
It is true that a minor extravasation causes only minor problems with sensitivity and comparisons to other scans, but it is difficult to determine the point at which an extravasation causes meaningful problems. Current practice strives to deliver a precisely known dose. For PET/CT procedures, after administering FDG, technologists flush the injection catheter with saline to wash the FDG into the vascular system, then measure the residual FDG in the injection syringe. While this residual amount is usually small (0.5% to 1.5% of the original dose), technologists subtract the residual radioactivity from the administered dose to ensure the scanner has an accurate “net dose”. The effect of an extravasation on the net dose will likely be higher than the residual dose in the injection syringe, but no steps are being taken today to address extravasations. Some nuclear medicine procedures use very low doses of activity for imaging. An extravasation of a small amount of administered activity, may have a meaningful effect on the image. Additionally, for therapy infusions, an extravasation results in patients not receiving the prescribed dose to the target.
Are extravasations tracked?
Extravasations are not often tracked. The following factors all contribute to the difficulty in tracking extravasations in current practice:

• The only way to track infiltrations today is to review images for extravasations. Nuclear medicine centers using a field of view from skull base to mid thighs will miss many extravasations. Only centers that always image the administration site can realize that extravasations have occurred.

• Reviewing past radiology reports is not an effective way to track extravasations, since visible extravasations (especially those considered to be minor) are not always reported by clinicians.

• When administering radiopharmaceuticals, technologists are often unaware that an extravasation has occurred and therefore do not follow the self-reporting guidelines, which advise imaging the administration site. The physical volume of most radiopharmaceuticals that a technologist administered into a patient is usually small; therefore, a visible manifestation of an extravasation is often not evident to the patient or the technologist. Finally, most radiopharmaceuticals do not usually cause the patient much, if any, discomfort so technologists are not alerted to a possible concern.
In the hospitals that have looked into this issue by reviewing every image, what is the rate of extravasations?
The average published radiopharmaceutical extravasation rate is 15.5% based on 8 studies* performed in 12 centers on 3354 patients.

*
  • Osman, M.M., et al., FDG dose extravasations in PET/CT: frequency and impact on SUV measurements. Front Oncol, 2011. 1: p. 41.
  • Hall, N., et al., Impact of FDG extravasation on SUV measurements in clinical PET/CT. Should we routinely scan the injection site? J Nucl Med, 2006. 47(suppl 1): p. 115P.
  • Bains, A., et al., Contamination in 18F-FDG PET/CT: an initial experience. J Nucl Med, 2009. 50 (supplement 2): p. 2222
  • Krumrey, S., et al., FDG manual injection verses infusion system: a comparison of dose precision and extravasation. J Nucl Med, 2009. 50(supplement 2): p. 2031.
  • Silva-Rodriguez, J., et al., Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies. Med Phys, 2014. 41(5): p. 052502.
  • Muzaffar, R., et al., Novel method to detect and characterize (18)F-FDG infiltration at the injection site: a single-institution experience. J Nucl Med Technol, 2017. 45(4): p. 267-271.
  • McIntosh, C. and J. Abele, Frequency of Interstitial Radiotracer Injection for Patients Undergoing Bone Scan, in The Canadian Association of Radiologists. 2016: Montreal, Quebec.
In centers that have used the Lara device to try and help the clinicians understand their administration quality, what is their rate of extravasations?
In the largest quality improvement project* that prospectively reviewed radiopharmaceutical extravasation rates, seven centers participated. Over 2,531 patients were monitored during the Measure Phase. Extravasation rates in these centers ranged from 2-16%. The authors stated that these results supported the results from the previously published retrospective studies.

In all, over 20 centers on three continents have used the Lara System to help them understand their injection quality. Many have published their results. Many have demonstrated that they can improve their administration quality by following well-known quality improvement processes. All of these results can be found in the Publications section on this website.

*
  • Wong, T.Z., et al., Quality Improvement Initiatives to Assess and Improve PET/CT Injection Infiltration Rates in Multiple Centers. J Nucl Med Technol, 2019. 47: p. 326-331.

Aren’t most of the reported extravasations minor?
Many centers note that the majority of the extravasations found on static images appear minor. The Lara system has monitored hundreds of extravasations; nearly every extravasation resolves (often dramatically) during the uptake period. An extravasation that appears minor at the end of uptake does not necessarily mean it was minor the whole time. The severity of extravasations is being understated in the current clinical setting.
What is the bottom line about the impact of diagnostic extravasations?
All extravasations irradiate patient tissue with unintentional irradiation and are not consistent with the nuclear medicine community’s effort to ensure that a patient’s dose is “as low as reasonably achievable” (ALARA). Significant extravasations can result in significant irradiation, which can lead to adverse tissue reaction effects and increases the patient’s chance of developing cancer. Additionally, since visible extravasations can be mischaracterized as minor and many extravasations are undiagnosed due to field of view limitations, clinicians can be unaware that their image results have been compromised. Extravasations represent an insidious source of patient harm and adds variance in nuclear medicine imaging that should be minimized, since these images can be critical for patient care and management decisions.
What is the bottom line about the impact of therapeutic extravasations?
Because therapeutic extravasations typically use very high doses of radiation, they can create serious patient harm by irradiating tissue at the extravasation site. Furthermore, the radiopharmaceutical left at the administration site is not reaching the intended target, thereby delivering less than the prescribed dose.
Will extravasations continue to be an important issue in the future?
Extravasations will have an even larger impact with the coming changes in medical practice. As we move towards more personalized, precision medicine, PET/CT and SPECT/CT are becoming progressively more quantitative. Extravasations invalidate the results of PET/CT and SPECT/CT scans used for quantification. Additionally, there is a movement towards exposing patients to radiation levels as low as reasonably achievable (ALARA), driving improved nuclear medicine scanners and lower prescribed doses. Extravasations leak a certain volume of the radiopharmaceutical into the subcutaneous tissue. With lower prescribed doses, the extravasated volume represents a larger percentage of the delivered dose than in the past, making extravasations even more concerning in the future.
How can we fix this extravasation problem?
Lucerno offers support for a comprehensive program for continuous quality improvement. The program starts with accurate measurement. Assessing how often extravasations really occur at a center is the first step to improving the problem. Only then can a center examine the circumstances that lead to extravasations and develop a plan to implement corrective actions to minimize extravasations in the future. After remediation plans have been instituted, new measurements should document improvement. This should cause a continuous and meaningful reduction in extravasation rates.
Will identifying extravasations lead to the complete elimination of extravasations?
It is unlikely that a process involving 2 humans performed 30 million times each year in the US can ever be perfect, but an extravasation rate approaching 1% should be possible. Trained infusion nurses administering chemotherapy agents through peripheral IV access, similar to radiopharmaceutical IV access methods, have lowered their extravasation rates to 0.18%. While certified nuclear medical technologists are committed to providing optimal imaging to their patients, they are not always trained to the same standards as infusion nurses. By using the Lara System to help identify each extravasation case and focusing on quality improvement, nuclear medicine centers should be able to reduce the extravasation rate below 1%. Even with such a low extravasation rate, clinicians and patients will still want to know which patients are affected by extravasations.