For this mini-review, PubMed was searched using the keywords and search terms highlighted in Table 1 with publication dates from the last twenty years (between 2003 and 2023). Initial search results yielded 512 publications, of which sixty-eight remained after removing duplicates and those articles not pertaining to radiopharmaceutical extravasations. Out of the sixty-eight publications, only two in the last twenty years were qualitative literature reviews assessing reporting prevalence of extravasation events in peer-reviewed publications. Most recently, van der Pol et al. published an extensive review of radiopharmaceutical extravasation literature and this review will not repeat that effort but will instead focus on highlighting recent trends and key gaps in research related to radiopharmaceutical extravasations (23). Figure 1 shows a word cloud rendering created from analysis of the frequency of words used in available reviewed publication abstracts providing a visual representation of common themes.

Only eight (12%) of the studies reviewed sample sizes of 100 patients or more and many of the publications were simple case studies of single events being reported (n=24, 35%). Diagnostic studies made up the majority of reports (n=36, 53%) followed by radionuclide therapy observations (n=17, 25%) and finally studies including both occurrences (n=9, 13%). Across the peer-reviewed research studies, a total of 9,786 patients were included with a total of 784 patients with an extravasation event recorded. The calculated average rate was eight percent across this group of publications and matches well with previous literature reviews and review articles that reviewed historic publications outside the scope of this work. This shows good consistency across independent assessments for a standardized rate of extravasation within these patient populations.

The depth of information related to extravasation occurrence, prevalence, and impact remains severely limited, however, there is a clear trend in increasing numbers of publications. In the first ten years reviewed there were a total of sixteen publications on extravasations and fifty-two in the subsequent ten year period representing growth of 225%. This potentially correlates with increased awareness and interest in this topic. Of particular note is an increase in the number of literature reviews and analyses of larger patient populations which help to enable more global assessment of common extravasation issues (21,23). Increased reporting through publications from institutions is critical to understanding the true impact of extravasations for both diagnostic and therapeutic radiopharmaceuticals.

There is also a notable trend in the creation and validation of tools designed to assess dosimetry related to extravasation events. Six of the sixty-eight publications included methodologies or tools for assessment of radiation dose to the patient at the site of the event representing approximately 9% of publications. Prior to 2017, only one publication had assessed extravasation dosimetry with four new publications on this topic since 2020. This is a growing area of interest both for the purpose of confirming diagnostic injection safety but to also have defined methods and tools for assessment of therapeutic events when they occur (25,26,28,30,31).

Common themes were observed across the studies reviewed in this work, but these commonalities also lead to additional unresolved questions.

The three most common elements were: •

Extravasations are a common clinical occurrence: The average rate of extravasation observed in this review was approximately eight percent. Using the European Medical Association definition for adverse effects, an occurrence of an event 1%–10% would be considered “common” (32,33). Assuming recent estimates for diagnostic nuclear imaging procedures is correct (13.5 million), then that indicates approximately one million patients per year may experience an extravasation event (34). This begs the question, “why is there a significant difference between reported infiltration rates for radiopharmaceutical injections (∼1%–8%) and chemotherapies (up to 6.5%), and why are reported rates far higher than those reported for modalities like CT and MRI (0.045%, 0.26%)? (13,16,18–20,24,35)”

While an increase in publications over the last twenty years suggests an increase in awareness, many fundamental questions related to radiopharmaceutical extravasation events remain unanswered. 1.

Standardization of reporting: Standardized reporting methods for radiopharmaceutical extravasations do not exist, which makes it difficult to compare data across studies and accurately assess the prevalence and impact of these events. Guidance documents that mention extravasations often only indicate that the event should be noted or was present, however, even the most rigorous quantitative recommendations only additionally suggest attempting to quantify residual activity at the site (7,9). Little guidance is found in the literature regarding the most appropriate or recommended consistent methodology for determination of the residual activity at the injection site in the event of extravasation.

A review of literature from the last twenty years reveals an increase in publications related to radiopharmaceutical extravasations. This suggests growing awareness of these events and their potential impact on patient care for imaging and therapy studies. Even with this increased volume of publications, there is still severely limited information related to principles that practitioners can apply in the clinic to make diagnostic and therapeutic decisions for their patients when these events occur. More research is needed across a wider range of radiopharmaceuticals and patient populations worldwide to determine consensus practice suggestions and to determine true clinical impact on imaging studies that use radiopharmaceuticals.