Bone metastases develop in most patients with metastatic castration-resistant prostate cancer (mCRPC). They affect the structural integrity of bone, manifesting as pain and skeletal-related events (SREs), and are the primary cause of patient disability, reduced quality of life (QOL) and death. Understanding the pathophysiology of bone metastases resulted in the development of agents that improve clinical outcome, suggesting that managing both the systemic disease and associated bone events is important. Historically, the treatment of CRPC bone metastases with early radiopharmaceuticals and external beam radiation therapy was largely supportive; however, now, zoledronic acid and denosumab are integral to the therapeutic strategy for mCRPC. These agents substantially reduce skeletal morbidity and improve patient QOL. Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease. Five other systemic agents are currently approved for use in mCRPC based on their ability to improve survival. These include the cytotoxic drugs docetaxel and cabazitaxel, the hormone-based therapies, abiraterone and enzalutamide, and the immunotherapeutic vaccine sipuleucel-T. Abiraterone and enzalutamide are able to reduce SREs and improve survival in this setting. Novel agents targeting tumour and bone cells are under clinical development.

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Bone is the single most frequent site for bone metastasis in breast cancer patients. Patients with bone-only metastasis have a fairly good prognosis when compared with patients with visceral disease. Nevertheless, cancer-induced bone disease carries an important risk of developing skeletal related events that impact quality of life (QoL). It is therefore particularly important to stratify patients according to their risk of developing bone metastasis. In this context, several risk factors have been studied, including demographic, clinicopathological, genetic, and metabolic factors. Most of them show conflicting or non-definitive associations and are not validated for clinical use. Nonetheless, tumour intrinsic subtype is widely accepted as a major risk factor for bone metastasis development and luminal breast cancer carries an increased risk for bone disease. Other factors such as gene signatures, expression of specific cytokines (such as bone sialoprotein and bone morphogenetic protein 7) or components of the extracellular matrix (like bone crosslinked C-telopeptide) might also influence the development of bone metastasis. Knowledge of risk factors related with bone disease is of paramount importance as it might be a prediction tool for triggering the use of targeted agents and allow for better patient selection for future clinical trials.

Different pyrazolyl-diamine ligands bearing anthracenyl or anthrapyrazole functionalities as DNA-binding groups, at different positions of the chelator framework, were labeled with the fac-[(99m)Tc(CO)(3)](+) core. The resulting complexes, 1-4, are highly stable in vitro under physiologic conditions; all of them have been identified by high-performance liquid chromatography comparison with the Re congeners, with the exception of 3, that is anchored by an anthrapyrazole diamine ligand. Aiming to assess the ability of these complexes to target the cell nucleus and to induce enhanced cell death by effect of the Auger electrons emitted by (99m)Tc, the intracellular distribution and radiotoxicity of 1-4 were evaluated by using B16F1 murine melanoma cells. The radiotoxic effects depend very much on the position used to introduce the DNA-binding group and are well correlated with the nuclear uptake of the compounds. Complex 2, having the anthracenyl substituent at the 4-position of the pyrazolyl ring, rapidly entered the cells and accumulated inside the nucleus, exhibiting the highest radiotoxic effects. This compound induced an apoptotic cellular outcome, and its enhanced radiotoxic effects were certainly due to the Auger electrons emitted by the radiometal in close proximity to DNA.