**Abstract**

In recent decades, multiple radiopharmaceutical conjugates have been tested and shown to be efficacious in treating metastasized castration-resistant prostate cancer (mCRPC). Several types of research have been published on the therapeutic use of α-emitter radiopharmaceuticals, and several authors suggested their treatment superiority. One of the suggested methods is targeted alpha therapy. In this method, alpha radiation delivers energy to cancer cells and the tumor microenvironment while minimizing toxicity to surrounding tissues. In this chapter, the alpha emitter radiopharmaceutical applications in castration-resistant prostate cancer patients were investigated. Hence, we studied the 223Ra and 225Ac α-emitter radiopharmaceuticals application method and distribution of dose throughout human body organs.

**Keywords:** radiopharmaceutical, treatment, alpha emitter, 223Ra, 225Ac, metastatic castration-resistant prostate cancer

## **1. Introduction**

The prostate gland weighs around 20 g and is located at the base of the bladder, near the prostatic urethra. It is split into four zones: peripheral, central, transitional, and peri-urethral. The most frequent location of prostate cancer in the peripheral zone, and adenocarcinoma accounts for the majority of cases, generally arising from acinar cells in the prostate gland and accompanied by a rise in serum prostatespecific antigen (PSA). PSA is unaffected by some tumor forms, including neuroendocrine tumors, small-cell carcinoma, and transitional cell carcinoma [1].

According to a study conducted in the United States, 241,740 men were diagnosed with prostate cancer in 2012, resulting in 28,170 fatalities. In the United States, about 160,000 men will be diagnosed with prostate cancer in 2017. Prostate cancer is the third largest cause of cancer mortality in males, despite its generally indolent course. Since 2011, there has been significant progress in finding treatment alternatives and defining illness risk [2].

Prostate cancer is the third most common cancer worldwide among males and the fourth in terms of incidence worldwide [3]. Patients with PCa may be treated with radical prostatectomy or radiation as initial therapies, although disease recurrence is possible. A prostatic-specific antigen (PSA) in the clinical setting of PCa screening has resulted in earlier detection. The first symptom of disease recurrence is an increase in PSA levels, referred to as biochemical recurrence (BR). Early recurrence can be treated with potentially curative salvage treatments such as additional lymphadenectomy or targeted radiation, although both need the disease to be localized [4].

Several radiopharmaceutical conjugates have been tried and proved to be effective in treating bone metastases [5–7] and metastasized castration-resistant prostate cancer in recent decades (mCRPC). In addition, various research on the therapeutic use of α-emitter radiopharmaceuticals have been published, and several writers have indicated that they are preferable in terms of therapy [8–16]. Targeted alpha treatment targets cancer cells and the tumor microenvironment while limiting damage to adjacent organs. Radiopharmaceuticals are specific radioisotope formulations used for diagnosis and treatment in important clinical domains. 223Ra and 225Ac radionuclides are the major radiopharmaceuticals utilized in treating prostate cancer [17].

The linear energy transfer (LET) causes damage to the cell DNA owing to the movement of the α-particle into the tissue, but the shortened range of the α-particle restricts tumor damage to the adjacent healthy cells, decreasing the damage. However, α particles may cause serious harm at both cellular and genetic levels, if breathed or eaten. External body exposure to an α-particle is insignificant. The possible harmful kind of radiation is α-particles [2].

Routines throughout the world include systemic chemotherapy, hormone therapies, and targeted bone drugs such as radium-223 dichloride (223Ra) and actinium-225 (225Ac) for skeleton metastases [18].

## **2. Radium-223**

223Ra (T1/2 = 11.43 day) is α-emitter radiopharmaceutical with an average energy of 5.78 MeV (accounting for 93.5 percent of emitted energy), 4% as particles, and 2% as radiation utilized in prostate cancer bone metastases. The dichloride-223Ra is a targeted emitter that binds to accelerated bone turnover in bone metastases and releases high-energy alpha particles with a short-range (100 m) [19, 20]. 223Ra treatment with a targeted-emitter provides radiation energy to cancer cells and tumor tissue while limiting damage to healthy tissues. **Table 1** shows 223Ra


**Table 1.** *The properties of 223Ra and 225Ac radiopharmaceuticals in the treatment of bone metastases prostate cancer.* *Radium-223 and Actinium-225 α-Emitter Radiopharmaceuticals in Treatment… DOI: http://dx.doi.org/10.5772/intechopen.99756*

radiopharmaceutical characteristics. Also, the decay chain of 223Ra radiopharmaceuticals is presented in **Figure 1**.

Radium-223 dichloride is a targeted alpha emitter that preferentially binds to regions where the bone turnover is enhanced in bones and produces short-range (<100 μm) high-energy alpha particulates. As osteoblastic calcium mimesis, 223Ra is linked into newly developed osteoblast or sclerotic metastasis, especially in the microenvironment. The high-energy radiation of alpha-particles leads largely to dual-stranded DNA breaks with a powerful and highly localized cytotoxic impact on the target areas. The alpha particles'short distance also minimizes the harmful effects on nearby healthy tissue, especially bone marrow [21].

In phase I and phase II trials involving bone metastasis patients, radium-223 has been shown to have a good safety profile with little myelotoxicity [22]. Studies of Phase two showed the reduction of pain and improvement of biomarkers associated with diseases (e.g., bone-alkaline phosphatase and prostate-specific antigen [PSA]) and suggest a survival advantage among patients who have castration-resistant prostate cancer and bone metastases [23]. In order to investigate radium-223's survival impact, we conducted a Phase 3 randomized, two-blind multi-national research that compared 223Ra effectiveness and safety to placebo in patients with

**Figure 1.** *The decay chain of 223Ra radiopharmaceuticals.*

castration-resistant prostate cancer and bone metastases in Symptomatic Prostate Cancer Painters (ALSYMPCA).
