Dataset Information

Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

ABSTRACT: The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n?=?47) or enzalutamide (n?=?33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P?=?0.001 and P?=?0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P?

SUBMITTER: Conteduca V

PROVIDER: S-EPMC5686214 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

Conteduca V V Scarpi E E Caroli P P Salvi S S Lolli C C Burgio S L SL Menna C C Schepisi G G Testoni S S Gurioli G G Paganelli G G Casadio V V Matteucci F F De Giorgi U U

Scientific reports 20171114 1

The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulatin ...[more]

PMID: 29138500

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Project description:The purpose of this study was to compare the diagnostic performance of 18F-DCFBC PET/CT, a first-generation 18F-labeled prostate-specific membrane antigen (PSMA)-targeted agent, and 18F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Methods: Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to 4 PET/CT scans. All patients completed baseline 18F-DCFBC PET/CT and 18F-NaF PET/CT scans, and 23 patients completed follow-up imaging, with a median follow-up interval of 5.7 mo (range, 4.2-12.6 mo). Lesion detection was compared across the 2 PET/CT agents at each time point. Detection and SUV characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using nonparametric statistical testing (Spearman correlation, Wilcoxon rank). Results: Twenty-six patients had metastatic disease detected on 18F-NaF or 18F-DCFBC at baseline, and 2 patients were negative on both scans. Three patients demonstrated soft tissue-only disease. Of 241 lesions detected at baseline, 56 were soft-tissue lesions identified by 18F-DCFBC only and 185 bone lesions detected on 18F-NaF or 18F-DCFBC. 18F-NaF detected significantly more bone lesions than 18F-DCFBC (P < 0.001). Correlation of PSA with patient-level SUV metrics was strong in 18F-DCFBC (? > 0.5, P < 0.01) and poor in 18F-NaF (? < 0.3, P > 0.1). When PSA levels were combined with treatment status, patients with below-median levels of PSA (<2 ng/mL) on androgen deprivation therapy (n = 11) demonstrated more lesions on 18F-NaF than 18F-DCFBC (P = 0.02). In PSA greater than 2 ng/mL, patients on androgen deprivation therapy (n = 8) showed equal to or more lesions on 18F-DCFBC than on 18F-NaF. Conclusion: The utility of PSMA-targeting imaging in metastatic prostate cancer appears to depend on patient disease course and treatment status. Compared with 18F-NaF PET/CT, 18F-DCFBC PET/CT detected significantly fewer bone lesions in the setting of early or metastatic castrate-sensitive disease on treatment. However, in advanced metastatic castrate-resistant prostate cancer, 18F-DCFBC PET/CT shows good concordance with NaF PET/CT.

Project description:BACKGROUND:Both enantiomers of [18F]flubatine are new radioligands for neuroimaging of ?4?2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[18F]flubatine compared to (-)-[18F]flubatine was its higher binding affinity suggesting that (+)-[18F]flubatine might be able to detect also slight reductions of ?4?2 nAChRs and could be more sensitive than (-)-[18F]flubatine in early stages of Alzheimer's disease. To support the clinical translation, we investigated a fully image-based internal dosimetry approach for (+)-[18F]flubatine, comparing mouse data collected on a preclinical PET/MRI system to piglet and first-in-human data acquired on a clinical PET/CT system. Time-activity curves (TACs) were obtained from the three species, the animal data extrapolated to human scale, exponentially fitted and the organ doses (OD), and effective dose (ED) calculated with OLINDA. RESULTS:The excreting organs (urinary bladder, kidneys, and liver) receive the highest organ doses in all species. Hence, a renal/hepatobiliary excretion pathway can be assumed. In addition, the ED conversion factors of 12.1 ?Sv/MBq (mice), 14.3 ?Sv/MBq (piglets), and 23.0 ?Sv/MBq (humans) were calculated which are well within the order of magnitude as known from other 18F-labeled radiotracers. CONCLUSIONS:Although both enantiomers of [18F]flubatine exhibit different binding kinetics in the brain due to the respective affinities, the effective dose revealed no enantiomer-specific differences among the investigated species. The preclinical dosimetry and biodistribution of (+)-[18F]flubatine was shown and the feasibility of a dose assessment based on image data acquired on a small animal PET/MR and a clinical PET/CT was demonstrated. Additionally, the first-in-human study confirmed the tolerability of the radiation risk of (+)-[18F]flubatine imaging which is well within the range as caused by other 18F-labeled tracers. However, as shown in previous studies, the ED in humans is underestimated by up to 50 % using preclinical imaging for internal dosimetry. This fact needs to be considered when applying for first-in-human studies based on preclinical biokinetic data scaled to human anatomy.

Dataset Information

Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

Publications

Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

Similar Datasets

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