PET radioligands are usually administered by intravenous (i.v.) injection in (ante)cubital fossa (elbow pit) or wrist. In clinical PET studies, patients may have fragile or poorly accessible veins, resulting occasionally in paravenous radioligand injections and dose extravasations (Boellaard et al, 2008; Boellaard, 2009; Osman et al, 2011; Silva-Rodriguez et al, 2014). In mouse studies PET tracer is usually injected into the mouse tail vein, which also often leads to extravasation (Vines et al., 2011; Lasnon et al., 2015). Part of the dose remains longer in the injection site, and is not being effectively administered, thus leading to overestimation of the actually administered dose (Boellaard et al, 2008; Silva-Rodriguez et al, 2014; Lee et al., 2016). Injected dose is used in SUV and total clearance calculations. Slow release of radiopharmaceutical from the injection site leads to flattening of input function and slow tissue uptake. If analysis method utilizes blood sampling, image-derived input function, or reference region, then the impact on results may be minimal if infiltration is not severe; clustering-based methods for input function estimation are very sensitive to the flattening of input function.

In human studies, extravasations are under-reported because the injection site is usually not included in the PET field-of-view. Considering this, Osman et al (2011) reported that extravasation is encountered in 1/10 of PET studies, and it caused marked underestimation in FDG SUV. Williams et al (2016) detected extravasation in 30% of FDG studies using a topical sensor, but injection site infiltration was resolved in some cases before the PET late-scan. In another sites, ∼2-16% infiltration rates was observed (Wong et al., 2019; Osborne et al., 2020). Procedure guideline for FDG PET (Boellaard et al, 2015) states that any problems with FDG administration must be reported, and if extravasation is suspected, then the injection area should be imaged. Administered dose can then be corrected for the "leaked" radioligand (Miyashita et al, 2007; Silva-Rodriguez et al, 2014). Topically applied sensors can be used to detect problems in injection (Lattanze et al., 2018; Knowland et al., 2019; Currie et al., 2020). Diagnostic imaging may be salvaged by delayed imaging, if extravasation is noticed in time (Kiser et al., 2018). Infusion pump systems may also be used to reduce the frequency of extravasations (Krumrey et al, 2009).

Somewhat similar problems may arise from venous stasis (Lattanze et al., 2018) and accidental intra-arterial injection (Bybel et al., 2003; Kumar, 2009; Zhu et al., 2011).

Extravasation may lead to intense radioactivity inside or outside of the PET field-of-view (for instance in the injection site or lymph node), which can cause overcorrection of scatter background, and that can lead to severe bias in region-of-interest radioactivity concentrations. Erthal et al (2017) reported a case where extravasation in 82Rb PET caused false-positive diagnosis of myocardial ischemia, until image was reconstructed again applying a limit for scatter correction.

Extravasation of PET radioligands does not cause harm to patients, but therapeutic radiopharmaceuticals may cause severe tissue lesions (van der Pol et al., 2017). Tissue dose estimation can then be used to determine whether surgical rinse is necessary (Tylski et al., 2021). Some formulations, especially with pH <5 or >9, may cause irritation if they leak into the tissue.

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Boellaard R, Oyen WJ, Hoekstra CJ, Hoekstra OS, Visser EP, Willemsen AT, Arends B, Verzijlbergen FJ, Zijlstra J, Paans AM, Comans EF, Pruim J. The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials. Eur J Nucl Med Mol Imaging 2008; 35(12): 2320-2333. doi: 10.1007/s00259-008-0874-2.

Boellaard R. Standards for PET image acquisition and quantitative data analysis. J Nucl Med. 2009; 50(Suppl 1): 11S-20S. doi: 10.2967/jnumed.108.057182.

Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, Verzijlbergen FJ, Barrington SF, Pike LC, Weber WA, Stroobants S, Delbeke D, Donohoe KJ, Holbrook S, Graham MM, Testanera G, Hoekstra OS, Zijlstra J, Visser E, Hoekstra CJ, Pruim J, Willemsen A, Arends B, Kotzerke J, Bockisch A, Beyer T, Chiti A, Krause BJ. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging 2015; 42(2): 328-354. doi: 10.1007/s00259-014-2961-x.

Hall NC, Zhang J, Reid R, Hurley D, Knopp MV. Impact of FDG extravasation on SUV measurements in clinical PET/CT. Should we routinely scan the injection site? J Nucl Med. 2006; 47: 115P.

Krumrey S, Frye R, Tran I, Yost P, Nguyen N, Osman M. FDG manual injection verses infusion system: a comparison of dose precision and extravasation. J Nucl Med. 2009; 50(Suppl 2): 2031.

Lasnon C, Dugué AE, Briand M, Dutoit S, Aide N. Quantifying and correcting for tail vein extravasation in small animal PET scans in cancer research: is there an impact on therapy assessment? EJNMMI Res. 2015; 5:61. doi: 10.1186/s13550-015-0141-z.

Lee JJ, Chung JH, Kim S-Y. Effect of 18-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses. Ann Nucl Med. 2016; 30: 525-533. doi: 10.1007/s12149-016-1090-y.

Miyashita K, Takahashi N, Oka T, Asakawa S, Lee J, Shizukuishi K, Inoue T. SUV correction for injection errors in FDG-PET examination. Ann Nucl Med. 2007; 21: 607-613. doi: 10.1007/s12149-007-0068-1.

Osman MM, Muzaffar R, Altinyay ME, Teymouri C. FDG dose extravasations in PET/CT: frequency and impact on SUV measurements. Front Oncol. 2011;1:41. doi: 10.3389/fonc.2011.00041.

Silva-Rodriguez J, Aguiar P, Sanchez M, Mosquera J, Luna-Vega V, Cortés J, Garrido M, Pombar M, Ruibal Á. Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies. Med Phys. 2014; 41(5): 052502. doi: 10.1118/1.4870979.

van der Pol J, Vöö S, Bucerius J, Mottaghy FM. Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review. Eur J Nucl Med Mol Imaging 2017; 44: 1234-1243. doi: 10.1007/s00259-017-3675-7.

Williams JM, Arlinghaus LR, Rani SD, Shone MD, Abramson VG, Pendyala P, Chakravarthy AB, Gorge WJ, Knowland JG, Lattanze RK, Perrin SR, Scarantino CW, Townsend DW, Abramson RG, Yankeelov TE. Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging. Eur J Nucl Med Mol Imaging 2016; 43: 2374-2380. doi: 10.1007/s00259-016-3477-3.

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Updated at: 2021-06-03
Created at: 2016-04-12
Written by: Vesa Oikonen