Questions and Answers

What is a radiotracer infiltration?
A radiotracer infiltration is the inadvertent administration of radiotracer anywhere outside the vascular compartment, such as into the subcutaneous tissue surrounding a vein.
How does an infiltration 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 injection, can cause the catheter tip to damage the vein wall.

During injection:
• Injecting radiotracer dose 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 injection site, can adversely impede the flow of the radiotracer 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 infiltrations.
Does an infiltration unintentionally expose arm tissue to radiation?
Absolutely. Dosimetry should be performed to estimate the equivalent dose to a volume of affected tissue.
Do infiltrations really matter to the results of a PET/CT scan?
Absolutely. An infiltration can have a major impact on both quantitative and qualitative PET/CT results.
How does an infiltration 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. Infiltrations invalidate quantitative PET/CT results.
How does an infiltration 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 injections, 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 venous system later in the uptake period. An infiltrated dose may leak back into the venous system during the uptake period and during image acquisition. Since infiltrations 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 infiltration results in degraded PET/CT images used by clinicians to stage and assess therapy.
Is it possible to assess infiltrations in PET/CT images and then correct the results?
In current practice the injection site is often not in the image field of view, so not all infiltrations are seen. When an infiltration 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 infiltration in a static image, Lucerno has found that this may not reflect the true extent of the infiltration at the time of the injection and during the entire uptake period.
Why aren’t injection sites in the field of view all the time? Is this a problem?
The most common practice is to have patients place their arms over their heads during a PET/CT scan. Since this field of view is from skull base to mid thighs, the injection site is often not visible to clinicians. If an injection site is not in the field of view and there is an infiltration, clinicians using the PET/CT results will be unaware that the image and SUVs are compromised.
If a clinician can see the injection site, why is it difficult to quantify the infiltration?
It is theoretically possible to quantify how much radiotracer is near the injection site if a trained professional is willing to trace its entire area on every axial slice of the image where an infiltration 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 infiltration be of limited value?
Lucerno has found that the amount of radiotracer present at the time of image capture (usually 60-90 minutes after the injection) may not be representative of the amount of FDG that was at the infiltrated injection site during the uptake period. In nearly every infiltration case that Lucerno has observed, the FDG at the injection 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 infiltration an hour or more after it occurs cannot adequately characterize the true nature and extent of the infiltration.
What if the infiltration is truly minor, does that matter to the dose and to the PET/CT results?
It is true that a minor infiltration causes only minor problems with sensitivity and comparisons to other scans, but it is difficult to determine the point at which an infiltration causes meaningful problems. Current practice strives to deliver a precisely known dose. After injecting 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 injected dose to ensure the scanner has an accurate “net dose”. The effect of an infiltration 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 infiltrations.
Are infiltrations tracked?
Infiltrations are not often tracked. The following factors all contribute to the difficulty in tracking FDG infiltrations in current practice:
• The only way to track infiltrations today is to review PET/CT images for infiltrations. Nuclear medicine centers using a field of view from skull base to mid thighs will miss many infiltrations. Only centers that always image the injection site can realize that infiltrations have occurred.
• Reviewing past radiology reports is not an effective way to track infiltrations, since visible infiltrations (especially those considered to be minor infiltrations) are not always reported by clinicians.
• When injecting FDG, technologists are often unaware that an infiltration has occurred and therefore do not follow the self-reporting guidelines, which advise imaging the injection site. The physical volume of FDG that a technologist injects into a patient is usually small; therefore, a visible manifestation of an infiltration is often not evident to the patient or the technologist. Finally, FDG does 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 infiltrations?
There are a limited number of publications on this topic, but a few hospitals have presented abstracts or articles on the rate of infiltrations. Ohio State University, St. Louis University, and the University of Santiago in Spain appear to be the leaders in this subject. These sites have presented results on over 2,000 patients, and the infiltration rates have averaged between 9% and 21%.
Aren’t most of the reported infiltrations minor?
Many centers note that the majority of the infiltrations found on static images appear small. However, Lucerno’s experience involving dozens of infiltrations is that nearly every infiltration resolves (often dramatically) during the uptake period, but small at the end of uptake does not necessarily mean the infiltration was small the whole time. This finding leads us to believe that the degree of infiltrations is being understated in the current clinical setting.
What is the bottom line about the impact of FDG infiltrations?
Since visible infiltrations can be mischaracterized as minor and many infiltrations are undiagnosed due to field of view limitations, clinicians are unaware their PET/CT results have been compromised. Lucerno believes that infiltrations represent an insidious source of variance in PET/CT images that should be minimized, since these images are critical for proper staging at the time of presentation and assessing therapy response during follow-up.
Are other nuclear medicine procedures also impacted by infiltrations?
Yes. Any nuclear medicine procedure that requires a bolus injection, can be affected by an infiltration. Additionally, radiotracers used in other nuclear medicine procedures can also expose patient arm tissue to unnecessary doses of radiation and need to be measured.
Will infiltrations continue to be an important issue in the future?
An infiltration will have an even larger impact with the coming changes in medical practice. As we move towards more personalized, precision medicine, PET/CT is becoming progressively more quantitative. An infiltration invalidates a PET/CT scan used for quantification. Additionally, there is a movement towards exposing patients to radiation levels as low as reasonably achievable (ALARA), driving improved PET/CT scanners and lower FDG doses. Infiltrations leak a certain volume of the FDG into the subcutaneous tissue. With lower FDG doses, this infiltrated volume represents a larger percentage of the delivered dose than in the past, making infiltrations even more concerning in the future.
How can we fix this FDG infiltration problem?
Lucerno offers support for a comprehensive program for continuous quality improvement. The program starts with accurate measurement. Assessing how often FDG infiltrations really occur at a center is the first step to improving the problem. Only then can a center examine the circumstances that lead to infiltrations and develop a plan to implement corrective actions to minimize infiltrations in the future. After remediation plans have been instituted, new measurements should document improvement. These new “best practices” should become standardized across centers to ensure that all benefit from this knowledge. This should cause a continuous and meaningful drop in FDG infiltration rates.
Will identifying FDG infiltrations lead to the complete elimination of infiltrations?
It is unlikely that a process involving 2 humans performed 18.5 million times each year in the US can ever be perfect, but an infiltration rate approaching 1% should be possible. Trained infusion nurses injecting chemotherapy agents have lowered their infiltration rates to ~1%. 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 infiltration case, focusing on sharing best practices, and establishing new standard techniques, nuclear medicine labs should be able to reduce the infiltration rate towards 1%. Even with such a low infiltration rate, clinicians will still want to know which 1% of patients are affected by infiltration.