Early 18F-FDHT PET/CT as a predictor of treatment response in mCRPC treated with enzalutamide.

232 Background: Androgen deprivation is the mainstay in the treatment of metastatic prostate cancer. During treatment, the majority of patients will develop progressive disease despite castrate levels of testosterone; castration-resistant prostate cancer (CRPC). In vivo determination of androgen receptor status by 18F-FDHT PET/CT could be of use to predict treatment response timely and objectively. The objective of this study is to assess the value of early 18F-FDHT PET/CT to predict treatment response of enzalutamide in mCRPC. Methods: This pilot study was performed in 18 chemotherapy naïve men with mCRPC. 18F-FDHT PET/CT was performed at baseline and after 4 weeks of treatment with enzalutamide. Standard Uptake Value (SUV)max and SUVpeak of the 5 most intense and/or all bone, pleura and lymph node metastases were determined per patient. Area under the curve (AUC), sensitivity (Se) and specificity (Sp) of different characteristics of 18F-FDHT PET/CT were performed by ROC analysis. Response was determined at 12 weeks of treatment according to PCCTWG. Results: A total of 477 lesions (411 bone, 3 pleura and 63 lymph node) were found. At 12 weeks, response was seen in 16 patients, whereas 2 patients showed no response. The characteristics of 18F-FDHT PET/CT are shown in table 1. Baseline median SUVpeak of all metastatic lesions showed an AUC of 0.79 to predict response. AUC values using the 5 most intense lesions only or using the delta between baseline and 5 weeks were less accurate. Clinical trial information: NTR4086. Conclusions: Baseline 18F-FDHT PET/CT using SUVpeak of all metastatic lesions predicts treatment response in mCRPC treated with enzalutamide with an AUC of 0.79.[Table: see text]

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Determining androgen inactivation status in prostate cancer by [18F] DHT PET.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.191 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 191-191

Author(s):

Ziqi Zhu ◽

Yoon-Mi Chung ◽

Olga Sergeeva ◽

Vladimir Kepe ◽

Michael Berk ◽

...

Keyword(s):

Prostate Cancer ◽

Retention Rate ◽

Xenograft Model ◽

Treatment Resistance ◽

Fold Increase ◽

Standard Uptake Value ◽

Retention Rates ◽

Castration Resistant Prostate Cancer ◽

Pet Ct

191 Background: Castration-resistant prostate cancer occurs in part due to increased tumor tissue testosterone (T) and dihydrotestosterone (DHT) that sustain tumor growth. T and DHT are converted to inactive T- and DHT-glucuronide (T/DHT-G) by uridine 5'-diphospho-glucuronosyltransferase family genes (UGT2B15 and UGT2B17) in glucuronidation-competent cells and excreted, but not in glucuronidation-deficient cells. Thus, low glucuronidation activity enables prostate tumors to preserve androgens, which increases hormone treatment resistance and may be detectable by functional imaging. Methods: We knocked out (KO) UGT2B15 and 17 in LNCaP cells and tested the DHT retention rate in the cell lines by pulse-chase using [3H]DHT as a probe. Free and DHT-G retention rates were separately determined after 5 to 60 min. To increase the signal difference between control and KO cells, we screened several ATP-binding cassette transporter inhibitors to block DHT-G excretion. We performed [18F]DHT PET/CT in castrated mice having a control and a KO xenograft on contralateral flanks ( n = 3). The ratio of the standard uptake value (SUV) in control to KO xenografts in each mouse was calculated. To increase the ratio between control and KO tumors, 50µg cyclosporin A (CSA) was injected 30 min before injecting [18F]DHT. Results: After 5 minutes of chase, control cells retained twice the DHT of KO cells. In control cells, 50%-70% DHT was glucuronidated. Almost no DHT-G was detected in KO cells, and free DHT was similar to control. Of the inhibitors, only CSA increased DHT-G (but not free DHT) in control cells, resulting in a 3-4-fold increase in overall signal. In vivo PET/CT showed control xenografts had higher peak SUV but also a higher elution rate. CSA increased the SUV ratio by 1.5-2. Conclusions: We developed a PET/CT modality to detect androgen inactivation in a prostate cancer xenograft model. Androgen-glucuronidation-proficient tumors give off a stronger signal that is increased by ATP transporter inhibition. Our method can provide a noninvasive means of determining androgen metabolism status and therefore could possibly predict effectiveness of potential therapies in a subgroup of tumors predisposed to androgen deprivation resistance.

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Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases

Frontiers in Oncology ◽

10.3389/fonc.2021.795712 ◽

2022 ◽

Vol 11 ◽

Author(s):

Chuan-Yu Sun ◽

Yuan-Yuan Mi ◽

Sheng-Yang Ge ◽

Qing-Feng Hu ◽

Ke Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Integrin Αvβ3 ◽

Integrin Receptors ◽

Secreted Expression ◽

Metastatic Lesions ◽

Promising Therapeutic Target ◽

Pet Ct

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvβ3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

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Machine learning for differentiating metastatic and completely responded sclerotic bone lesion in prostate cancer: a retrospective radiomics study

British Journal of Radiology ◽

10.1259/bjr.20190286 ◽

2019 ◽

Vol 92 (1101) ◽

pp. 20190286 ◽

Cited By ~ 6

Author(s):

Emine Acar ◽

Asım Leblebici ◽

Berat Ender Ellidokuz ◽

Yasemin Başbınar ◽

Gamze Çapa Kaya

Keyword(s):

Prostate Cancer ◽

Machine Learning ◽

Texture Analysis ◽

Area Under The Curve ◽

Ct Images ◽

Metastatic Lesions ◽

Psma Pet ◽

Pet Ct ◽

Sclerotic Lesions ◽

Psma Expression

Objective:Using CT texture analysis and machine learning methods, this study aims to distinguish the lesions imaged via 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT as metastatic and completely responded in patients with known bone metastasis and who were previously treated.Methods:We retrospectively reviewed the 68Ga-PSMA PET/CT images of 75 patients after treatment, who were previously diagnosed with prostate cancer and had known bone metastasis. A texture analysis was performed on the metastatic lesions showing PSMA expression and completely responded sclerotic lesions without PSMA expression through CT images. Textural features were compared in two groups. Thus, the distinction of metastasis/completely responded lesions and the most effective parameters in this issue were determined by using various methods [decision tree, discriminant analysis, support vector machine (SVM), k-nearest neighbor (KNN), ensemble classifier] in machine learning.Results:In 28 of the 35 texture analysis findings, there was a statistically significant difference between the two groups. The Weighted KNN method had the highest accuracy and area under the curve, has been chosen as the best model. The weighted KNN algorithm was succeeded to differentiate sclerotic lesion from metastasis or completely responded lesions with 0.76 area under the curve. GLZLM_SZHGE and histogram-based kurtosis were found to be the most important parameters in differentiating metastatic and completely responded sclerotic lesions.Conclusions:Metastatic lesions and completely responded sclerosis areas in CT images, as determined by 68Ga-PSMA PET, could be distinguished with good accuracy using texture analysis and machine learning (Weighted KNN algorithm) in prostate cancer.Advances in knowledge:Our findings suggest that, with the use of newly emerging software, CT imaging can contribute to identifying the metastatic lesions in prostate cancer.

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Accurate Monitoring of the Response of Bone Metastases to Treatment in Patients with Prostate Cancer Using Choline PET/CT

Case Reports in Oncology ◽

10.1159/000514191 ◽

2021 ◽

pp. 520-524

Author(s):

Kazuhiro Kitajima ◽

Shingo Yamamoto ◽

Masayuki Fujiwara ◽

Yusuke Kawanaka ◽

Yusuke Yamada ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Metabolic Response ◽

Choline Uptake ◽

Castration Resistant Prostate Cancer ◽

Choline Pet ◽

Metastatic Lesions ◽

Radium 223 ◽

Positron Emission ◽

Pet Ct

We here report 2 cases of castration-resistant prostate cancer (CRPC) observed two times on 11C-choline positron emission tomography computed tomography (PET/CT), which was useful to discriminate viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and to determine the viability of bone metastases, regardless of whether sclerosis was present or not. Because one case demonstrated disappearance of abnormal 11C-choline uptake of osteoblastic metastatic lesions after abiraterone therapy and no new lesions at other sites, suggesting nonviable bone metastases, we can assume a complete metabolic response. Because the other case demonstrated a decrease in the existing, abnormal 11C-choline uptake of osteoblastic metastatic lesions, but multiple new appearances of osteoblastic and nonosteoblastic lesions with abnormal 11C-choline uptake after radium-223 therapy suggesting multiple viable bone metastases, we can assume progressive metabolic disease. 11C-choline PET/CT could help in assessing the treatment response of bone metastases in patients with metastatic CRPC.

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Exploring Spatial-Temporal Changes in 18F-Sodium Fluoride PET/CT and Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer Treated With Enzalutamide

Journal of Clinical Oncology ◽

10.1200/jco.20.00348 ◽

2020 ◽

Vol 38 (31) ◽

pp. 3662-3671

Author(s):

Christos E. Kyriakopoulos ◽

Elisabeth I. Heath ◽

Anna Ferrari ◽

Jamie M. Sperger ◽

Anupama Singh ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Response ◽

Bone Lesion ◽

Specific Antigen ◽

Standardized Uptake Value ◽

Ct Scans ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Pet Ct ◽

Psa Progression

PURPOSE Intrapatient treatment response heterogeneity is under-recognized. Quantitative total bone imaging (QTBI) using 18F-NaF positron emission tomography/computed tomography (PET/CT) scans is a tool that allows characterization of interlesional treatment response heterogeneity in bone. Understanding spatial-temporal response is important to identify individuals who may benefit from treatment beyond progression. PATIENTS AND METHODS Men with progressive metastatic castration-resistant prostate cancer (mCRPC) with at least two lesions on bone scintigraphy were enrolled and treated with enzalutamide 160 mg daily (ClinicalTrials.gov identifier: NCT02384382 ). 18F-NaF PET/CT scans were obtained at baseline (PET1), week 13 (PET2), and at the time of prostate-specific antigen (PSA) progression, standard radiographic or clinical progression, or at 2 years without progression (PET3). QTBI was used to determine lesion-level response. The primary end point was the proportion of men with at least one responding bone lesion on PET3 using QTBI. RESULTS Twenty-three men were enrolled. Duration on treatment ranged from 1.4 to 34.1 months. In general, global standardized uptake value (SUV) metrics decreased while on enzalutamide (PET2) and increased at the time of progression (PET3). The most robust predictor of PSA progression was change in SUVhetero (PET1 to PET3; hazard ratio, 3.88; 95% CI, 1.24 to 12.1). Although overall functional disease burden improved during enzalutamide treatment, an increase in total burden (SUVtotal) was seen at the time of progression, as measured by 18F-NaF PET/CT. All (22/22) evaluable men had at least one responding bone lesion at PET3 using QTBI. CONCLUSION We found that the proportion of progressing lesions was low, indicating that a substantial number of lesions appear to continue to benefit from enzalutamide beyond progression. Selective targeting of nonresponding lesions may be a reasonable approach to extend benefit.

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Abstract 1077: Genomic alterations in plasma cell-free DNA predict treatment response to abiraterone acetate and prednisone and survival in metastatic castration-resistant prostate cancer

10.1158/1538-7445.am2018-1077 ◽

2018 ◽

Author(s):

Meijun Du ◽

Manish Kohli ◽

Chiang-Ching Huang ◽

Liang Wang

Keyword(s):

Prostate Cancer ◽

Treatment Response ◽

Plasma Cell ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

Genomic Alterations ◽

Cell Free Dna ◽

Castration Resistant ◽

Free Dna ◽

Predict Treatment Response

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Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

Medicine ◽

10.1097/md.0000000000026206 ◽

2021 ◽

Vol 100 (23) ◽

pp. e26206

Author(s):

Kazuhiro Kitajima ◽

Shingo Yamamoto ◽

Yusuke Kawanaka ◽

Hisashi Komoto ◽

Kimihiro Shimatani ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Treatment Response ◽

Castration Resistant Prostate Cancer ◽

Choline Pet ◽

Castration Resistant ◽

Pet Ct

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The prognostic power of 18F-FDG PET/CT extends to estimating systemic treatment response duration in metastatic castration-resistant prostate cancer (mCRPC) patients

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00391-8 ◽

2021 ◽

Author(s):

Matteo Bauckneht ◽

Francesco Bertagna ◽

Maria Isabella Donegani ◽

Rexhep Durmo ◽

Alberto Miceli ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Response ◽

Fdg Pet ◽

Prognostic Value ◽

Systemic Treatment ◽

Response Duration ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Background We aimed to test whether the prognostic value of 18 F‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration. Methods mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration. Results We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy. Conclusions FDG-PET/CT’s prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.

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