Radiopharmaceuticals in Modern Cancer Therapy

*Aisyah Elliyanti*

#### **Abstract**

Nuclear medicine plays a role in oncology. It uses tracers (radiopharmaceuticals) to study physiological processes and treat diseases. The radiopharmaceuticals can be formed as radionuclides alone or radionuclides labeled with other molecules as a drug, a protein, or a peptide. The radiopharmaceutical is introduced into the body and accumulates in the target tissue of interest for therapy or imaging purposes. It offers to study cancer biology in vivo to optimize cancer therapy. Another advantage of radiopharmaceutical therapy is a tumor-targeting agent that deposits lethal radiation at tumor sites. This review outlines radiopharmaceuticals agents in current cancer therapy.

**Keywords:** radionuclides, beta particles, alpha particles, auger electron, radioimmunotherapy, peptide receptor radionuclide therapy

### **1. Introduction**

Usage of radiopharmaceuticals has increased in recent decades, mainly for the treatment of cancer diseases [1]. However, the oncology community is still unfamiliar with radiopharmaceutical therapy (RPT). Compared with all other systemic cancer treatment options, radiopharmaceuticals have an efficacy result with minimal toxicity [2]. The radiopharmaceutical therapy application introduces new tumor-targeting agent therapy, different from external radiotherapy (**Figure 1**). It quantifies radioactivity distribution in tumor sites and in vivo detection [2]. The advantages of RPT are: firstly, it is targeted into tumor, included metastasis sites. Secondly, the high linear energy transfer (LET) radionuclides are effectively killed the radioresistant hypoxic cells. Thirdly, relatively lower whole-body absorbed dose [3–5]. The therapy might be used as adjuvant therapy with or after other treatment options such as chemotherapy and surgery [6, 7]. In controlling the symptoms, shrink and stabilize the tumors for systemic metastatic cancer, where conventional radiotherapy or chemotherapy is impossible, RPT can be a choice, especially for patients who no longer respond to other treatments [2, 6].

The radiopharmaceuticals can be in the form of radionuclides alone or radionuclides labeled (radiolabeled) for imaging or therapy. They can be labeled with molecules such as a drug, a protein, or a peptide for the therapy. Physical and biochemical characteristics of radiopharmaceuticals/radionuclides should be considered for treatment purposes. The physical characters are included physical half-life, energy radiation(s), type of emissions, daughter product(s), production method, and radionuclide purity [6, 8]. The biochemical characteristic includes tissue targeting, radioactivity retention in the tumor, in vivo stability, toxicity and the

#### **Figure 1.**

*Radiopharmaceutical therapy versus external radiotherapy. In RPT, radionuclide has administrated intravenous delivery to the targeted tumor. The tumor cells will receive an absorbed dose which is exponentially decreasing over the period. The dose is delivered per cell by emissions originating from cells is influenced by the range of the emissions. When the range of the emitted particle is much longer than the dimension of the cell, periphery tumor cells of tumor mass will receive absorbed dose and crossfire dose from other target cells, and it caused a crossfire dose to normal tissue. However, the response of the normal cell will differ from the tumor cell (a). In external radiotherapy, radiation delivers the same absorbed dose per cell regardless the number of cells (b).*

effective half-life within the patient's body [2]. A convenience range of the physical half-life of radionuclide is between 6 hours and seven days [9]. A very short physical half-life has a limitation due to the delivery time, and a long half-life of radiopharmaceuticals will expose the surrounding environment to more time radiation. The physical half-life should not too long, but it should have sufficient retention time. So, the radiation can be delivered to the tumor efficiently [1]. On the other hand, when the biological half-life is too short, the radionuclide will be discharged with significantly high activity. Therefore, for efficient radiation delivery for therapy

#### *Radiopharmaceuticals in Modern Cancer Therapy DOI: http://dx.doi.org/10.5772/intechopen.99334*

purposes, a balanced optimal biological and physical half-life should be considered, besides the type of tumor, method of administration, and uptake mechanism [1, 6]. Radionuclides radiations as alpha (α)-particle (50–230 keV/μm) and beta (β)-particle (0.2 keV/μm), and Äuger electrons (4–26 keV/μm) are used for therapy purposes [1, 3, 6, 10, 11]. These particles allow ionization per travel length, and they are fully deposited within a small range of tissue. The distance traveled, and the energy deposited in cells is vital that lead the most efficient route for cell destruction is the direct interaction of ionization events with DNA.

Some β-emitter radionuclides also decay γ-particle, which is used for imaging. Radionuclides that emit α or β-particles are preferred for the treatment of bulky solid tumors, and radionuclides that emit Äuger electrons are considered for the treatment of tiny clusters of cancer cells or small tumor deposits because of their high-level cytotoxicity and short-range biological effectiveness [3]. The other factor that needs to be considered is the daughter product of the radionuclides. If the daughter product is unstable, it should be short-life and may decay within hours into a stable product, and un-stable daughter nuclide will contribute to the amount of absorbed dose. Radiopharmaceuticals' biochemical characteristics are selective tumor target concentrations and have optimal retention time in the tumor and avoid uptake in the normal cells [6, 9]. Depending on the tumor uptake mechanism, either by bone deposition, protein binding, or metabolic uptake, the ratio concentration of radionuclides on the tumor to normal tissues should be as optimal as possible [6]. The other factors that have to be considered are the radionuclides particles' size, low toxicity, specific gravity for optimal flow and distribution, and clearance rate [6, 12–16].

Iodine-131 (131I) was one of the first radionuclides used for therapy in clinical oncology, especially for thyroid cancer patients. Phosphorous-32 (32P), strontium-89 ( 89Sr), and yttrium-90 (90Y) also have been used for the treatment of benign and malignant diseases [6, 17, 18]. Various alpha- and beta-radiation-emitting isotopes are used lately. Most of them are labeled with peptides and antibodies for specific tumor targeting, where radiopharmaceuticals are used as vehicles to deliver ionizing radiation to the tumor tissue. This review discusses radiopharmaceuticals are used for therapy and their application in the modern era of cancer therapy.
