Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called “theranostic” approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC

Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer

“…Given that the majority of pivotal trials in mHSPC and mCRPC have been conducted using standard imaging for staging, limited evidence is available regarding the potential predictive role of PET tracers during the staging and re-staging of patients with prostate cancer. Several PET-derived parameters might be of value for the prognostic stratification of patients with mCRPC before systemic therapy [ 160 ]. In addition, PET imaging might better reflect treatment response and may allow one to avoid useless toxicity in resistant patients and switch them earlier to more effective therapeutic options.…”

Recent Advances in Brachytherapy Using Radioactive Nanoparticles: An Alternative to Seed-Based Brachytherapy

“…Radiolabeling strategy to achieve the maximal radiochemical purity and yield, which reflects specific activity of nanoradiopharmaceuticals Among the different types of nanoparticles, AuNPs and iron oxide nanoparticles (IONPs) have gained more prominence due to their superior biocompatibility, low toxicity, ease in surface versatile functionalization and radiolabeling with a plethora of imaging, and therapeutic radionuclides towards the development of nanoradiopharmaceuticals for imaging and therapy of cancer. Translational medicine that makes use of nanoradiopharmaceutical agents demonstrates excellent pharmacokinetics in terms of radiochemical production, purity and stability (nanoradioformulation integrity), biodistribution, dosimetry, low off-target localization, and favorable renal clearance profiles, which represent a versatile theranostic tool in cancer management, ranging from nuclear medicine imaging and image-guided surgery to alpha/beta-particle targeted therapy, and most recently targeted nanobrachytherapy (18)(19)(20)(21). The use of targeted nanobrachytherapy through radiolabeled nanoparticles affords intra-or peritumoral administration, thus allowing less invasiveness and homogenizing the radiation dose deposition in the tumor as compared with conventional BT (22).…”

“…Indirect radiolabeling via chelators is susceptible to in vivo radiometal trans-chelation with native biological chelators and ions as well as metalloenzymes, transport, and storage proteins in the body. This problem is evaded by radiolabeling with nonmetallic radionuclides covalently bound to nanoparticles through prosthetic groups ( 11 C, 14 C, 18 F, 123 I, 124 I, 125 I, and 131 I) (25). [ 18 F]-Fluoro-2-deoxy-D-glucose ( 18 F-FDG) is used for the assessment of glycolysis as a non-invasive PET imaging agent.…”

“…[ 18 F]-Fluoro-2-deoxy-D-glucose ( 18 F-FDG) is used for the assessment of glycolysis as a non-invasive PET imaging agent. In an archetypical example, radiolabeling nanoparticles with 18 F has been reported by first conjugating cysteamine to mannose triflate (Man-CA) and then 18 F labeling resulting to a cysteamine-linked radiotracer ( 18 F-FDG-CA). The 18 F-FDG-CA is mixed with gold chloride (HAuCl 4 ) to obtain AuNPs ( 18 F-FDG-CA-AuNPs) (32).…”

[99Tc]Sestamibi Bioaccumulation Induces Apoptosis in Prostate Cancer Cells: an in Vitro Study

“…Similarly, no/rare biological targets are available for precision therapy. In the last years, several researchers focused their attention of the evaluation of PSMA inhibitors as possible drugs capable to eradicate prostate cancer lesions also blocking cancer progression [3][4][5]. Some of these PSMA inhibitors are also radiolabeled and used to perform in vivo evaluation of prostate cancers in nuclear medicine departments [3][4][5].…”