Assessment of Simplified Methods for Quantification of <sup>18</sup>F-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

Krämer, G.; Yaqub, Maqsood; Vargas, Hebert Alberto; Schuit, Robert C.; Windhorst, Albert D.; Eertwegh, Alfons J.M. van den; Veldt, Astrid A.M. van der; Bergman, Andries M.; Burnazi, Eva; Lewis, Jason S.; Chua, Sue; Staton, Kevin D.; Beattie, Bradley J.; Humm, John L.; Davis, Ian D.; Weickhardt, Andrew; Scott, Andrew M.; Morris, Michael J.; Hoekstra, Otto S.; Lammertsma, Adriaan A.

doi:10.2967/jnumed.118.220111

Cited by 13 publications

(22 citation statements)

References 23 publications

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“…A potential advantage of normalization to the parent plasma input curves is that the uptake metrics are corrected for any treatment-induced or other changes in the radiotracer's metabolism, albeit at the expense of an additional dynamic PET scan, venous blood samples, and metabolite analysis. Moreover, including an additional variable into uptake metric calculations can increase uncertainty (14,21), although in the present study, SUV AUCpp did not significantly affect overall variability of any of the SUV metrics on a lesion level. One outlier was seen with unexplained large differences in whole-blood activity concentrations between test and retest scans, which could not be accounted for by sample measurement errors, suggesting the need for caution in the case of response assessment.…”

Section: Normalization To Parent Plasma Input Curvecontrasting

confidence: 62%

“…Other studies also using SUV max -based thresholds showed similar results (22,23), yet a significant decrease in repeatability was seen when only lesions of 4.2 mL or less were included in the analysis. Studies have also shown decreased variability when evaluating repeatability on a per-patient (as opposed to a per-lesion) basis (14,21).…”

Section: Discussionmentioning

confidence: 99%

“…Two studies have shown a correlation (R 2 : 0.6-0.7) between nonlinear regression analysis of dynamic 18 F-FDHT data and SUV (5,14). Additionally, preliminary results showed a nearperfect correlation when the SUV was normalized to the AUC (R 2 : 0.99).…”

Section: Normalization To Parent Plasma Input Curvementioning

confidence: 92%

“…The following 18 F-FDHT uptake metrics were recorded: SUV max , SUV peak (1.2 cm 3 spheric region positioned within the lesion to maximize its mean value), and SUV mean (all voxels within the lesion) corrected for body weight. Additionally, these metrics were normalized to the area under the parent plasma time-activity concentration curve (AUC) at 30 min (SUV AUCpp ) (14). Androgen receptor-positive tumor volume ([ARTV] derived using a 50% threshold of SUV max corrected for local background) and total lesion uptake ([TLU] defined as SUV mean • ARTV) of 18 F-FDHT were calculated.…”

Section: Data Management and Analysismentioning

confidence: 99%

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Reproducibility and Repeatability of Semiquantitative ¹⁸F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

et al. 2018

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F-fluorodihydrotestosterone (F-FDHT) is a radiolabeled analog of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer. We conducted a prospective multiinstitutional study of metastatic castration-resistant prostate cancer patients undergoing 2 (test/retest)F-FDHT PET/CT scans on 2 consecutive days. Two independent readers evaluated all examinations and recorded SUVs, androgen receptor-positive tumor volumes, and total lesion uptake for the most avid lesion detected in each of 32 predefined anatomic regions. The relative absolute difference and reproducibility coefficient (RC) of each metric were calculated between the test and retest scans. Linear regression analyses, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to evaluate repeatability of F-FDHT metrics. The coefficient of variation and ICC were used to assess interobserver reproducibility. Twenty-seven patients with 140 F-FDHT-avid regions were included. The best repeatability amongF-FDHT uptake metrics was found for SUV metrics (SUV SUV, and SUV), with no significant differences in repeatability among them. Correlations between the test and retest scans were strong for all SUV metrics ( ≥ 0.92; ICC ≥ 0.97). The RCs of the SUV metrics ranged from 21.3% (SUV) to 24.6% (SUV). The test and retest androgen receptor-positive tumor volumes and TLU, respectively, were highly correlated ( and ICC ≥ 0.97), although variability was significantly higher than that for SUV (RCs> 46.4%). The prostate-specific antigen levels, Gleason score, weight, and age did not affect repeatability, nor did total injected activity, uptake measurement time, or differences in uptake time between the 2 scans. Including the most avid lesion per patient, the 5 most avid lesions per patient, only lesions 4.2 mL or more, only lesions with an SUV of 4 g/mL or more, or normalizing of SUV to area under the parent plasma activity concentration-time curve did not significantly affect repeatability. All metrics showed high interobserver reproducibility (ICC > 0.98; coefficient of variation < 0.2%-10.8%). Uptake metrics derived fromF-FDHT PET/CT show high repeatability and interobserver reproducibility.

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Section: Normalization To Parent Plasma Input Curvecontrasting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Normalization To Parent Plasma Input Curvementioning

confidence: 92%

Section: Data Management and Analysismentioning

confidence: 99%

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Reproducibility and Repeatability of Semiquantitative ¹⁸F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

et al. 2018

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“…Furthermore, SUV might not be the best quantification method for 18 F-FDHT uptake. In a small study with 4 metastatic prostate cancer patients, SUV corrected for plasma 18 F-FDHT concentration showed a better correlation (27).…”

Section: Discussionmentioning

confidence: 88%

Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

et al. 2017

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In addition to the well-known estrogen receptor (ER) and human epidermal growth factor receptor 2, the androgen receptor (AR) is also a potential drug target in breast cancer treatment. Whole-body imaging can provide information across lesions within a patient. ER expression in tumor lesions can be visualized by F-fluoroestradiol (F-FES) PET, and AR expression has been visualized in prostate cancer patients with F-fluorodihydrotestosterone (F-FDHT) PET. Our aim was to assess the concordance between F-FDHT andF-FES PET and tumor AR and ER expression measured immunohistochemically in patients with metastatic breast cancer. Patients with ER-positive metastatic breast cancer were eligible for the study, irrespective of tumor AR status. The concordance ofF-FDHT and F-FES uptake on PET with immunohistochemical expression of AR and ER in biopsies of corresponding metastases was analyzed. Patients underwentF-FDHT PET and F-FES PET. A metastasis was biopsied within 8 wk of the PET procedures. Tumor samples with more than 10% and 1% nuclear tumor cell staining were considered, respectively, AR- and ER-positive. Correlations between PET uptake and semiquantitative immunohistochemical scoring (percentage positive cells × intensity) were calculated. The optimum threshold of SUV to discriminate positive and negative lesions for both AR and ER was determined by receiver-operating-characteristic analysis. In the 13 evaluable patients, correlation ( ) between semiquantitative AR expression and F-FDHT uptake was 0.47 ( = 0.01) and between semiquantitative ER expression and F-FES uptake 0.78 ( = 0.01). The optimal cutoff for AR-positive lesions was an SUV of 1.94 for F-FDHT PET, yielding a sensitivity of 91% and a specificity of 100%; the optimal cutoff was an SUV of 1.54 for F-FES PET, resulting in a sensitivity and specificity of 100% for ER.F-FDHT and F-FES uptake correlate well with AR and ER expression levels in representative biopsies. These results show the potential use of whole-body imaging for receptor status assessment, particularly in view of biopsy-associated sampling errors and heterogeneous receptor expression in breast cancer metastases.

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PET and SPECT Imaging of Steroid Hormone Receptors in the Brain

Moraga-Amaro

Doorduin

Dierckx

et al. 2020

PET and SPECT of Neurobiological Systems

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Steroid hormones, like sex hormones and corticosteroids, are involved in normal brain function. They can influence behavior and higher functions via binding to the corresponding hormone receptors. Steroid hormones also play a crucial role in psychiatric disorders by interacting with different neurotransmitter systems in the brain. Most of the studies in this field have been performed on postmortem

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Assessment of Simplified Methods for Quantification of ¹⁸F-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

Cited by 13 publications

References 23 publications

Reproducibility and Repeatability of Semiquantitative ¹⁸F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

Reproducibility and Repeatability of Semiquantitative ¹⁸F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

PET and SPECT Imaging of Steroid Hormone Receptors in the Brain

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Assessment of Simplified Methods for Quantification of 18F-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

Cited by 13 publications

References 23 publications

Reproducibility and Repeatability of Semiquantitative 18F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

Reproducibility and Repeatability of Semiquantitative 18F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

Androgen and Estrogen Receptor Imaging in Metastatic Breast Cancer Patients as a Surrogate for Tissue Biopsies

PET and SPECT Imaging of Steroid Hormone Receptors in the Brain

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Product

Resources

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Assessment of Simplified Methods for Quantification of ¹⁸F-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

Reproducibility and Repeatability of Semiquantitative ¹⁸F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study

Reproducibility and Repeatability of Semiquantitative ¹⁸F-Fluorodihydrotestosterone Uptake Metrics in Castration-Resistant Prostate Cancer Metastases: A Prospective Multicenter Study