Molecular radiotheragnostics in prostate cancer

Abstract

Two different molecular radio-theragnostic principles are applied in prostate cancer, providing a personalised management for those patients. Firstly, radiopharmaceuticals with the same or similar mechanism of action but different energy (gamma-γ, eg 99m Tc-diphosphonates or positron-β+, eg 18F-NaF emitting isotopes) can be used to identify patients with osteoblastic metastases for a treatment with bone seeking beta (β-) or alpha (α-) emitting radionuclides to deliver targeted molecular radiotherapy. IntroductionProstate cancer is the most common cancer in men, affecting approximately 1 in 9 males. It is also the second most common cause of cancer death in males in the UK, accounting for approximately 13% of all cancer deaths in males. 1 Almost all patients dying from prostate cancer today have castrationresistant prostate cancer (CRPC) and patients with CRPC have a 90-95% probability of developing bone metastases, which lead to severe morbidity -including bone pain, pathological fractures, spinal cord compression and haematological consequences of bone marrow infiltration. 2-5Because of the importance of bone metastases in overall disease progression and quality of life, bone targeted therapy constitutes an essential part of the treatment of CRPC. Clinically, management of bone metastases requires a multidisciplinary approach. Moderate bone pain is usually controlled by conventional analgesics, following the World Health Organization 'three step ladder'; localised pain could be treated effectively with ABSTRACT Molecular radiotheragnostics in prostate cancerexternal beam radiotherapy. However, a substantial amount of patients experience widespread multifocal bone metastases where the above measures become less useful. [3][4][5][6] Two classes of agents are specially targeting bone metastases in prostate cancer: targeting bone resorption and bone-seeking radiopharmaceuticals. Zoledronic acid is a bisphosphonate that delays skeletal-related events (SREs) by inhibiting osteoclast mediated bone resorption. Denosumab is a human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), which has proven to be more effective than zolendronic acid for SRE prevention. These treatments, however, do not have direct tumouricidal effects and have demonstrated limited symptomatic relief.3-8 Over the past several decades, bone-seeking radiopharmaceuticals have demonstrated their value in diagnosing and treating painful bone metastases.In addition, a new radiolabelled theragnostic compound targeting prostate-specific membrane antigen (PSMA) has been developed to select patients and deliver irradiation to all tumour sites, including osseous, nodal and visceral metastases. Radiotheragnostic pathway for metastatic bone diseaseThe patient selection process for targeted bone therapy follows a theragnostic pathway, which involves the same theragnostic Key pointsProstate cancer is the most common cancer in men, leading to approximately 13% of cancer deaths in men Bone is the most common metastatic site ...

Novel Biological and Molecular Characterization in Radiopharmaceutical Preclinical Design

“…In fact, the ability to image, quantify and characterize radionuclides with different emission properties, as well as β- and α-particles, enables activity distribution at microscopic scale of therapeutic compounds to be resolved, ensuring a biological response and toxicity prediction in dosimetry analysis of all radiopharmaceutical studies [ 10 , 11 ].…”