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Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used for primary staging in prostate cancer (PC), mainly because of its improved accuracy in detecting lymph node metastases compared with conventional imaging. However, the diagnostic benefit of PSMA PET/CT for detecting bone metastases is less well established. This study compares the diagnostic accuracy of 18 F-PSMA PET/CT and 18 F-NaF PET/CT for detecting bone metastases in patients newly diagnosed with PC. Methods: This prospective study included patients with histologically confirmed high-risk PC. All participants were referred from the department of urology to 18 F-NaF PET/CT and underwent 18 F-PSMA PET/CT within 3 weeks. Images were reviewed by 2 nuclear medicine physicians unaware of the results of the other imaging modality. Presence or absence of bone metastases and number of metastatic lesions were recorded. A reference standard was established at the patient level based on agreement between the 2 imaging modalities. In cases of concordance, both modalities were deemed correct. In cases of discordance, additional follow-up scans were performed. Diagnostic performance metrics, including sensitivity, specificity, and accuracy, were calculated. Results: In total, 160 participants were included. Sensitivity, specificity, and accuracy for detecting bone metastases at the patient level were 0.98, 0.99, and 0.99, respectively, for 18 F-PSMA PET/CT, and 0.91, 1.00, and 0.97, respectively, for 18 F-NaF PET/CT. No significant differences were found. The concordance rate of bone metastases between 18 F-NaF and 18 F-PSMA PET/CT at the patient level was observed in 154 patients (96.3%). 18 F-PSMA PET/CT tended to identify more bone metastases per patient than 18 F-NaF PET/CT. Conclusion: Both 18 F-NaF and 18 F-PSMA PET/CT exhibit high diagnostic accuracy for detecting bone metastases in newly diagnosed high-risk PC patients. 18 F-PSMA PET/CT may detect additional metastatic lesions compared with 18 F-NaF PET/CT. Subsequent 18 F-NaF PET/CT may be redundant if no bone metastases are found on 18 F-PSMA PET/CT., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: We evaluated the prognostic value of 18F-sodium fluoride (NaF) PET/CT in patients with urological malignancies treated with cabozantinib and nivolumab with or without ipilimumab. Methods: We prospectively recruited patients with advanced urological malignancies into a phase I trial of cabozantinib plus nivolumab with or without ipilimumab. NaF PET/CT scans were performed pre- and 8 weeks post-treatment. We measured the total volume of fluoride avid bone (FTV) using a standardized uptake value (SUV) threshold of 10. We used Kaplan-Meier analysis to predict the overall survival (OS) of patients in terms of SUVmax, FTV, total lesion fluoride (TLF) uptake at baseline and 8 weeks post-treatment, and percent change in FTV and TLF. Result: Of 111 patients who underwent NaF PET/CT, 30 had bone metastases at baseline. Four of the 30 patients survived for the duration of the study period. OS ranged from 0.23 to 34 months (m) (median 6.0 m). The baseline FTV of all 30 patients ranged from 9.6 to 1570 ml (median 439 ml). The FTV 8 weeks post-treatment was 56–6296 ml (median 448 ml) from 19 available patients. Patients with higher TLF at baseline had shorter OS than patients with lower TLF (3.4 vs 14 m; p = 0.022). Patients with higher SUVmax at follow-up had shorter OS than patients with lower SUVmax (5.6 vs 24 m; p = 0.010). However, FTV and TLF 8 weeks post-treatment did not show a significant difference between groups (5.6 vs 17 m; p = 0.49), and the percent changes in FTV (12 vs 14 m; p = 0.49) and TLF (5.6 vs 17 m; p = 0.54) also were not significant. Conclusion: Higher TLF at baseline and higher SUVmax at follow-up NaF PET/CT corresponded with shorter survival in patients with bone metastases from urological malignancies who underwent treatment. NaF PET/CT may be a useful predictor of OS in this population. [ABSTRACT FROM AUTHOR]

Background: Inconclusive bone scans are a challenge but there is no consensus about follow-up imaging. We evaluated the use of 68gallium-labelled prostate-specific membrane antigen (68Ga-PSMA) PET/CT if 18F-sodium fluoride (18F-NaF) PET/CT was inconclusive. Methods: This retrospective study included patients with no previously known bone metastases who had one or more equivocal bone lesions on 18F-NaF PET/CT and underwent additional 68Ga-PSMA PET/CT. The bone lesions were deemed as true metastases or not based on follow-up by surveying supplemental imaging modalities and hospital records. A subgroup of patients with “most valid follow-up” was created, which included patients with unmeasurable PSA after prostatectomy or subsequent imaging (additional 18F-NaF PET/CT, 68Ga-PSMA PET/CT, CT, or MRI). Results: Of the 2918 patients referred for 18F-NaF PET/CT from the department of urology in the inclusion period, 51 (1.7%) were inconclusive regarding bone metastases and underwent additional 68Ga-PSMA PET/CT. Thirteen of these patients (25%) were ultimately diagnosed with bone metastases. Patient-based sensitivity, specificity, and accuracy of additional 68Ga-PSMA PET/CT were 100%, 95%, and 96%, respectively. In patients with “most valid follow-up”, the same parameters were 100%, 93%, and 94%, respectively. Conclusion: 68Ga-PSMA PET/CT is an excellent complementary modality in when 18F-NaF PET/CT is equivocal.

Our purpose was to validate a semiautomatic quantification of the skeletal tumor burden on 18F-fluoride PET/CT using manual quantification as a reference. Methods: We quantified 51 18F-fluoride PET/CT examinations performed on female breast cancer patients. Clinical information (age; time of disease presentation; presence of visceral metastases; and time to death, progression, or a bone event) was recorded. The total volume of 18F-fluoride-avid skeletal metastases and the total activity of 18F-fluoride-avid metastases were calculated manually and semiautomatically. Results: Manual and semiautomatic metrics correlated strongly (P < 0.0001; 95% confidence interval, 0.9300-0.9769). On multivariable analysis, the semiautomatic measures of total activity for 18F-fluoride-avid metastasis correlated significantly with overall survival (P = 0.0001) and progression-free survival (P = 0.0006). Approximate times for calculating skeletal tumor burden (semiautomatic vs. manual) were, respectively, 30 s versus 321 s in patients with fewer than 5 metastases, 120 s versus 640 s in patients with 5-10 metastases, and 240 s versus 1207s in patients with more than 10 metastases. Conclusion: Semiautomatic quantification of whole-body 18F-fluoride PET/CT skeletal tumor burden can replace manual quantification in breast cancer patients and is a strong independent biomarker of prognosis. [ABSTRACT FROM AUTHOR]

Objective. Manual disease delineation in full-body imaging of patients with multiple metastases is often impractical due to high disease burden. However, this is a clinically relevant task as quantitative image techniques assessing individual metastases, while limited, have been shown to be predictive of treatment outcome. The goal of this work was to evaluate the efficacy of deep learning-based methods for full-body delineation of skeletal metastases and to compare their performance to existing methods in terms of disease delineation accuracy and prognostic power. Approach. 1833 suspicious lesions on 37 18 F-NaF PET/CT scans of patients with metastatic castration-resistant prostate cancer (mCRPC) were contoured and classified as malignant, equivocal, or benign by a nuclear medicine physician. Two convolutional neural network (CNN) architectures (DeepMedic and nnUNet ) were trained to delineate malignant disease regions with and without three-model ensembling. Malignant disease contours using previously established methods were obtained. The performance of each method was assessed in terms of four different tasks: (1) detection, (2) segmentation, (3) PET SUV metric correlations with physician-based data, and (4) prognostic power of progression-free survival. Main Results. The nnUnet three-model ensemble achieved superior detection performance with a mean (+/- standard deviation) sensitivity of 82.9±ccc 0.1% at the selected operating point. The nnUnet single and three-model ensemble achieved comparable segmentation performance with a mean Dice coefficient of 0.80±0.12 and 0.79±0.12, respectively, both outperforming other methods. The nnUNet ensemble achieved comparable or superior SUV metric correlation performance to gold-standard data. Despite superior disease delineation performance, the nnUNet methods did not display superior prognostic power over other methods. Significance. This work showed that CNN-based (nnUNet) methods are superior to the non-CNN methods for mCRPC disease delineation in full-body 18 F-NaF PET/CT. The CNN-based methods, however, do not hold greater prognostic power for predicting clinical outcome. This merits more investigation on the optimal selection of delineation methods for specific clinical tasks., (© 2023 Institute of Physics and Engineering in Medicine.)

Background: Inconclusive bone scans are a challenge but there is no consensus about follow-up imaging. We evaluated the use of 68gallium-labelled prostate-specific membrane antigen (68Ga-PSMA) PET/CT if 18F-sodium fluoride (18F-NaF) PET/CT was inconclusive. Methods: This retrospective study included patients with no previously known bone metastases who had one or more equivocal bone lesions on 18F-NaF PET/CT and underwent additional 68Ga-PSMA PET/CT. The bone lesions were deemed as true metastases or not based on follow-up by surveying supplemental imaging modalities and hospital records. A subgroup of patients with "most valid follow-up" was created, which included patients with unmeasurable PSA after prostatectomy or subsequent imaging (additional 18F-NaF PET/CT, 68Ga-PSMA PET/CT, CT, or MRI). Results: Of the 2918 patients referred for 18F-NaF PET/CT from the department of urology in the inclusion period, 51 (1.7%) were inconclusive regarding bone metastases and underwent additional 68Ga-PSMA PET/CT. Thirteen of these patients (25%) were ultimately diagnosed with bone metastases. Patient-based sensitivity, specificity, and accuracy of additional 68Ga-PSMA PET/CT were 100%, 95%, and 96%, respectively. In patients with "most valid follow-up", the same parameters were 100%, 93%, and 94%, respectively. Conclusion: 68Ga-PSMA PET/CT is an excellent complementary modality in when 18F-NaF PET/CT is equivocal. [ABSTRACT FROM AUTHOR]

Our purpose was to validate a semiautomatic quantification of the skeletal tumor burden on 18 F-fluoride PET/CT using manual quantification as a reference. Methods: We quantified 51 18 F-fluoride PET/CT examinations performed on female breast cancer patients. Clinical information (age; time of disease presentation; presence of visceral metastases; and time to death, progression, or a bone event) was recorded. The total volume of 18 F-fluoride-avid skeletal metastases and the total activity of 18 F-fluoride-avid metastases were calculated manually and semiautomatically. Results: Manual and semiautomatic metrics correlated strongly ( P < 0.0001; 95% confidence interval, 0.9300-0.9769). On multivariable analysis, the semiautomatic measures of total activity for 18 F-fluoride-avid metastasis correlated significantly with overall survival ( P = 0.0001) and progression-free survival ( P = 0.0006). Approximate times for calculating skeletal tumor burden (semiautomatic vs. manual) were, respectively, 30 s versus 321 s in patients with fewer than 5 metastases, 120 s versus 640 s in patients with 5-10 metastases, and 240 s versus 1207s in patients with more than 10 metastases. Conclusion: Semiautomatic quantification of whole-body 18 F-fluoride PET/CT skeletal tumor burden can replace manual quantification in breast cancer patients and is a strong independent biomarker of prognosis., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: The aim of this article is to present examples in which sodium fluoride labelled with 18 F (NaF) bone PET/CT would be a useful adjunct to guide complex clinical decisions about the staging, restaging, and treatment approach for patients with skeletal metastases and benign causes of NaF activity that can be mistaken for bone metastases. We present a pictorial review of selected cases of this cohort of patients., Conclusion: NaF PET/CT hybrid fusion imaging is extremely useful in identifying potential causes of pain in patients with malignancies that have an affinity for skeletal metastases. This technique can help detect bone metastases, in problem solving, and to direct appropriate management.

The aim of this study was to prospectively compare planar, bone scan (BS) versus SPECT/CT and NaF PET/CT in detecting bone metastases in prostate cancer. Thirty-seven consecutive, newly diagnosed, prostate cancer patients with prostate specific antigen (PSA) levels ≥ 50 ng/mL and who were considered eligible for androgen-deprivation therapy (ADT) were included in this study. BS, SPECT/CT, and NaF PET/CT, were performed prior to treatment and were repeated after six months of ADT. Baseline images from each index test were independently read by two experienced readers. The reference standard was based on a consensus decision made by a multidisciplinary team on the basis of baseline and follow-up images of the index tests, the findings of the baseline index tests by the experienced readers, and any available imaging, biochemical, and clinical data, including the response to ADT. Twenty-seven (73%) of the 37 patients had bone metastases according to the reference standard. The sensitivities for BS, SPECT/CT and NaF PET/CT were 78%, 89%, and 89%, respectively, and the specificities were 90%, 100%, and 90%, respectively. The positive predictive values of BS, SPECT/CT and NaF PET/CT were 96%, 100%, and 96%, respectively, and the negative predictive values were 60%, 77% and 75%, respectively. No statistically significant difference among the three imaging modalities was observed. All three imaging modalities showed high sensitivity and specificity. NaF PET/CT and SPECT/CT showed numerically improved, but not statistically superior, sensitivity compared with BS in this limited and selected patient cohort., Competing Interests: None.

Purpose: In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease., Results: Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p < 0.0001) and progression free-survival (p < 0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448)., Materials and Methods: We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months., Conclusions: 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

Unlabelled: This prospective pilot study evaluated the ability of Na(18)F PET/CT to detect and monitor bone metastases over time and its correlation with clinical outcomes and survival in advanced prostate cancer., Methods: Sixty prostate cancer patients, including 30 with and 30 without known bone metastases by conventional imaging, underwent Na(18)F PET/CT at baseline, 6 mo, and 12 mo. Positive lesions were verified on follow-up scans. Changes in SUVs and lesion number were correlated with prostate-specific antigen change, clinical impression, and overall survival., Results: Significant associations included the following: SUV and prostate-specific antigen percentage change at 6 mo (P = 0.014) and 12 mo (P = 0.0005); SUV maximal percentage change from baseline and clinical impression at 6 mo (P = 0.0147) and 6-12 mo (P = 0.0053); SUV change at 6 mo and overall survival (P = 0.018); number of lesions on Na(18)F PET/CT and clinical impression at baseline (P < 0.0001), 6 mo (P = 0.0078), and 12 mo (P = 0.0029); and number of lesions on Na(18)F PET/CT per patient at baseline and overall survival (P = 0.017). In an exploratory analysis, paired (99m)Tc-methylene diphosphonate bone scans ((99m)Tc-BS) were available for 35 patients at baseline, 19 at 6 mo, and 14 at 12 mo (68 scans). Malignant lesions on Na(18)F PET/CT (n = 57) were classified on (99m)Tc-BS as malignant 65% of the time, indeterminate 25% of the time, and negative 10% of the time. Additionally, 69% of paired scans showed more lesions on Na(18)F PET/CT than on (99m)Tc-BS., Conclusion: The baseline number of malignant lesions and changes in SUV on follow-up Na(18)F PET/CT significantly correlate with clinical impression and overall survival. Na(18)F PET/CT detects more bone metastases earlier than (99m)Tc-BS and enhances detection of new bone disease in high-risk patients., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: The purpose of this study was to define a method to assess skeletal tumor burden with 18F-labeled sodium fluoride PET/CT (18F-fluoride PET/CT) and evaluate the reproducibility of these measurements., Methods: Ninety-eight consecutive patients (90 men; mean age±SD, 65.7±14.2 y) underwent 158 18F-fluoride PET/CT scans for evaluation of skeletal metastatic disease. In order to determine the mean normal bone SUV, initially a 1-cm spheric volume of interest (VOI) was placed over 5 bone sites: T12, L5, sacrum, right iliac bone, and right femur. For each patient, the mean SUVmax for all sites was generated. Afterward, a threshold value of normal bone uptake was established. Subsequently, skeletal tumor burden was determined by generating volumetric data using a whole-body segmentation method. Any SUVmax below the normal threshold was excluded from analysis, as were VOIs not related to metastatic disease. Statistics for the remaining VOIs were then generated and defined as the skeletal metastatic tumor burden by 2 parameters: total lesion fluoride uptake above an SUVmax of 10 (TLF10) and fluoride tumor volume above an SUVmax of 10 (FTV10). TLF10 and FTV10 reproducibility was determined using 2 independent and experienced PET/CT interpreters analyzing a subset of 13 18F-fluoride PET/CT scans., Results: Mean (±SD) normal bone SUVmax was 6.62±1.55 for T12, 6.11±1.73 for L5, 4.59±1.74 for sacrum, 5.39±1.72 for right iliac bone, and 3.90±1.57 for right femur. The mean normal SUVmax for all 543 sites was 5.32±0.99. On the basis of these values, an SUVmax threshold of 10 was chosen to exclude normal bone from the volumetric calculations. Semiautomated measurements of TLF10 and FTV10 exhibited high interobserver reproducibility, within ±0.77% and ±3.62% of the interinterpreter average for TLF10 and FTV10, respectively., Conclusion: Determination of skeletal tumor burden with 18F-fluoride PET/CT is feasible and highly reproducible. Using an SUVmax threshold of 10 excludes nearly all normal bone activity from volumetric calculations., Competing Interests: No other potential conflict of interest relevant to this article was reported., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: The purpose of this study was to evaluate outcome after (223)Ra dichloride therapy ((223)Ra) and to determine whether skeletal tumor burden on whole-body (18)F-fluoride PET/CT can be used as a predictive biomarker of survival in patients treated with (223)Ra., Methods: Forty-two patients with hormone-refractory prostate cancer underwent (223)Ra and a baseline fluoride PET/CT scan. Fluoride PET/CT parameters were generated, including maximum standardized uptake value (SUVmax) of the hottest lesion (hSUVmax), average SUV of disease (Mean10), and skeletal tumor burden indices of total fluoride skeletal metastatic lesion uptake (TLF10) and total volume of fluoride avid bone metastases (FTV10). Overall survival (OS) was the primary endpoint. Secondary endpoints were progression-free survival and skeletal-related event (SRE)., Results: Skeletal tumor burden indices (TLF10 and FTV10) derived from fluoride PET/CT at baseline were highly correlated and significant independent predictors of OS (P = 0.0212; hazard ratio = 5.990; 95% confidence interval = 1.306-27.475). A TLF10 cutoff value of 8,000 discriminated survivors from nonsurvivors after (223)Ra (with TLF10 values < 8,000, the median OS was not estimated, whereas with TLF10 > 8,000, the median OS was 6.67 mo). Visual analysis, Mean10, and hSUVmax were not predictors of OS or progression-free survival. Mean10 was found to be a significant univariate predictor of the odds of having an SRE (P = 0.0445; odds ratio = 1.30; 95% confidence interval = 1.006-1.681), with a Mean10 greater than 19 increasing the risk of SRE., Conclusion: Skeletal tumor burden on baseline fluoride PET/CT is a predictive biomarker of OS and the risk of an SRE in patients treated with (223)Ra., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)