Repeatability of <sup>18</sup>F-FDG Uptake Measurements in Tumors: A Metaanalysis

Langen, Adrianus J. de; Vincent, Andrew; Velasquez, Linda; Tinteren, Harm van; Boellaard, Ronald; Shankar, Lalitha; Boers, Maarten; Smit, Egbert F.; Stroobants, Sigrid; Weber, Wolfgang; Hoekstra, Otto S.

doi:10.2967/jnumed.111.095299

Cited by 147 publications

(145 citation statements)

References 26 publications

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“…In summary, we show that the magnitude of changes in SUV mean of EGFR PET probes and HER3 PET probes induced by treatment with the PI3K inhibitor GDC-0941 or the AKT inhibitor GDC-0068 differ both according to cell line and according to treatment type when tested in a panel of breast cancer cell xenografts. Furthermore, we note that the magnitude of imaged changes in the xenograft models (as measured by SUV mean ) would be readily interpretable in clinical practice (23,24). The potential therapeutic relevance of our results is highlighted by the findings of Tao et al (9), in which they demonstrate both the upregulation of EGFR and HER3 with PI3K/ AKT pathway inhibition and the therapeutic benefit of adding EGFR/HER3 inhibitors to PI3K/AKT inhibitors.…”

Section: Discussionmentioning

confidence: 55%

Differential Receptor Tyrosine Kinase PET Imaging for Therapeutic Guidance

et al. 2016

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Inhibitors of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway hold promise for the treatment of breast cancer, but resistance to these treatments can arise via feedback loops that increase surface expression of the receptor tyrosine kinases (RTK) epidermal growth factor receptor 1 (EGFR) and human epidermal growth factor receptor 3 (HER3), leading to persistent growth pathway signaling. We developed PET probes that provide a method of imaging this response in vivo, determining which tumors may use this escape pathway while avoiding the need for repeated biopsies. Methods: Anti-EGFR-F(ab′) 2 and anti-HER3-F(ab′) 2 were generated from monoclonal antibodies by enzymatic digestion, conjugated to DOTA, and labeled with 64 Cu. A panel of breast cancer cell lines was treated with increasing concentrations of the AKT inhibitor GDC-0068 or the PI3K inhibitor GDC-0941. Pre-and posttreatment expression of EGFR and HER3 was compared using Western blot and correlated to probe accumulation with binding studies. Nude mice xenografts of HCC-70 or MDA-MB-468 were treated with either AKT inhibitor or PI3K inhibitor and imaged with either EGFR or HER3 PET probe. Results: Changes in HER3 and EGFR PET probe accumulation correlate to RTK expression change as assessed by Western blot (R 2 of 0.85-0.98). EGFR PET probe PET/CT imaging of HCC70 tumors shows an SUV of 0.32 ± 0.03 for vehicle-, 0.50 ± 0.01 for GDC-0941-, and 0.62 ± 0.01 for GDC-0068-treated tumors, respectively (P , 0.01 for both comparisons to vehicle). HER3 PET probe PET/ CT imaging of MDAMB468 tumors shows an SUV of 0.35 ± 0.02 for vehicle-and 0.73 ± 0.05 for GDC-0068-treated tumors (P , 0.01). Conclusion: Our imaging studies, using PET probes specific to EGFR and HER3, show that changes in RTK expression indicative of resistance to PI3K and AKT inhibitors can be seen within days of therapy initiation and are of sufficient magnitude as to allow reliable clinical interpretation. Noninvasive PET monitoring of these RTK feedback loops should help to rapidly assess resistance to PI3K and AKT inhibitors and guide selection of an appropriate combinatorial therapeutic regimen on an individual patient basis.

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Section: Discussionmentioning

confidence: 55%

Differential Receptor Tyrosine Kinase PET Imaging for Therapeutic Guidance

et al. 2016

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“…A possible explanation is the unusually high tumor uptake in this patient population (average SUV max , 15.0). De Langen et al (28) have shown that SUV repeatability improves with increasing tumor uptake, possibly because of a higher signal-to-noise ratio in these high-uptake regions of the image. Most of the papers included in this review did not directly address this issue, and their results reflect the average repeatability over a broad range of tumor uptake values.…”

Section: Discussionmentioning

confidence: 99%

“…Table 1 shows the articles that were identified and included in this review. Sixteen papers (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), published between 1995 and 2016, met the inclusion criteria. All were reports on original research, although there was some overlap in the source data: Nakamoto et al (22) (28) performed a metaanalysis pooling data from 5 previously published cohorts.…”

Section: Suv Repeatability Literaturementioning

confidence: 99%

Repeatability of SUV in Oncologic ¹⁸F-FDG PET

2017

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Learning Objectives: On successful completion of this activity, participants should be able to (1) describe the way test-retest studies have been used to measure SUV repeatability, (2) summarize the different methodologic approaches and complexities when analyzing SUV test-retest data, and (3) understand the implications of SUV repeatability for the quantitative assessment of tumor response to treatment.Financial Disclosure: This work was partially funded by grants from the National Institutes of Health (HHSN268201300071C and U01CA140204). The author of this article has indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA category 1 credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through April 2020.Quantitative analysis can potentially improve the accuracy and consistency of 18 F-FDG PET, particularly for the assessment of tumor response to treatment. Although not without limitations, SUV has emerged as the predominant metric for tumor quantification with 18 F-FDG PET. Growing literature suggests that the difference between SUVs measured before and after treatment can be used to predict tumor response at an early stage. SUV is, however, associated with multiple sources of variability, and to best use SUV for response assessment, an understanding of the repeatability of the technique is required. Test-retest studies involve repeated scanning of the same patient on the same scanner using the same protocol no more than a few days apart and provide basic information on the repeatability of the technique. Multiple test-retest studies have been performed to assess SUV repeatability, although a comparison of reports is complicated by the use of different methodologies and statistical metrics. This article reviews the available data, addressing issues such as different repeatability metrics, relative units, log transformation, and asymmetric limits of repeatability. When acquired with careful attention to protocol, tumor SUV has a withinsubject coefficient of variation of approximately 10%. In a response assessment setting, SUV reductions of more than 25% and increases of more than 33% are unlikely to be due to measurement variability. Broader margins may be required for sites with less rigorous protocol compliance, but in general, SUV is a highly repeatable imaging biomarker that is ideally suited to monitoring tumor response to treatment in individual patients.

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“…This alternative measure of the highest activity within a tumor was introduced due to the major limitation of SUV max , that is, the high variability introduced by the statistical noise associated with a single voxel analysis. As has been shown in phantom and dynamic patient studies, this statistical noise substantially impairs the repeatability of SUV max [27][28][29]. Averaging the values of a number of voxels within a given VOI, as proposed by SUV peak [30,31], can reduce this noise and therefore increases the repeatability without significant reduction of reproducibility.…”

Section: Repeatability Of Suv Measurementsmentioning

confidence: 95%