Radiomics and theranostics with molecular and metabolic probes in prostate cancer: toward a personalized approach

ABSTRACT

Introduction

In the last decade, two new radionuclide-based therapies, ²²³Radichloride and radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA), have been approved by the regulatory authorities for the management of castrate-resistant prostate cancer (PCa).

Areas covered

The basic principles of PCa molecular imaging are illustrated, with a particular attention to the combined use of diagnosis and therapy in a unique approach (the so-called theranostics) for response prediction and assessment in patients submitted to ²²³Radichloride or PSMA targeted therapies. In this perspective, the potential of radiomics, an emerging discipline based on the extraction of quantitative features from medical images, is covered.

Expert opinion

Theranostic metabolic and molecular probes have been successfully applied to predict and monitor response to radionuclide-based therapies. In particular, both ^99mTc-MDP and ¹⁸F-NaF resulted useful tools for personalized dosimetry and prognostic stratification before ²²³Ra-therapy, while PSMA-ligands, alone or in combination with ¹⁸F-FDG, provided valuable information to select patients who are more likely to benefit from RLT and getting information on PCa grade of differentiation and aggressiveness. In spite of its high potential, PET-radiomics for PCa is still at an embryonic phase and needs further validation.

KEYWORDS:

• Prostate cancer
• theranostics
• single photon emission tomography
• positron emission computed tomography
• precision medicine
• targeted therapy
• artificial intelligence
• radiomics

Article highlights

• In the last decade ²²³Ra-dichloride and radioligand therapy (RLT) targeting prostate specific membrane antigen (PSMA) have been approved by the regulatory authorities for the management of metastatic castration-resistant prostate cancer (mCRPCa).

• Theranostic and radiomic approaches have been applied in mCRPCa patients submitted to ²²³Ra-dichloride and PSMA-RLT in order to achieve optimal pre-treatment selection.

• Both bone scintigraphy with ^99mTc-labeled phosphonates and PET/CT with ¹⁸F-fluoride (¹⁸F-NaF) proved useful for provisional dosimetry, prognostication and response assessment to ²²³Ra-therapy, while PET-based radiomics has not found relevant applications in this specific field.

• PET/CT or PET/MRI with PSMA-ligands (⁶⁸Ga-PSMA or ¹⁸F-PSMA) represent a mandatory first-step to select patients before RLT with ¹⁷⁷Lu-PSMA or ²²⁵Ac-PSMA. However, about 30% of mCRPCa subjects do not respond to RLT in spite of PSMA-avid lesions detected on pre-therapeutic PET scan.

• Radiomic models gave promising results to differentiate responders from non-responders and predict biochemical response and survival after PSMA-RLT.

• Preliminary scientific reports highlight the importance of performing dual-tracer PET/CT with PSMA and ¹⁸F-fluorodexoyglucose (¹⁸F-FDG) for patients’ selection before PSMA-RLT, since ¹⁸F-FDG can be employed as a biomarker of PCa dedifferentiation and aggressiveness.

• Furthers studies are needed to better define the most appropriate use of the different molecular and metabolic probes (i.e. single-tracer or combined multi-tracer modality) for PCa theranostics and to validate and implement radiomic approaches in this specific clinical setting.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Author contributions

L.F., L.E. and L.U. designed the review study; F.B., M.C.M. and B.P. performed the literature research and data extraction; L.F., L.U., L.E. and F.B. wrote the paper; L.E. and O.S. supervised the paper.

Additional information

Funding

This paper was not funded.