The most commonly used equipment, which is used to make nuclear medicine, is the generator. The most commonly used nuclides used in nuclear medicine is 99 m-Tc (^99mTc) which is produced in a highly shielded column of fission product Mo-99 (⁹⁹Mo-parent) bound to alumina (Al₂O₃). The ⁹⁹Tc (daughter) is milked (eluted) by drawing sterile saline through the column into the vacuum vile. The parent ⁹⁹Mo is firmly bound to alumina, and as a result, the eluted ^99mTc contains negligible amounts of ⁹⁹Mo, and the daughter ⁹⁹Tc, which is washed away with saline, is collected in a vile (vacuum). From the sterile solution containing ^99mTc, sodium pertechnetate injection is prepared for applications into the body organs and remains on the column. The generator is called a cow; the daughter nuclide is referred to as milking and surrounding lead shield is called a pig (Fig. 9.3). The ^99mTc decays to ⁹⁹Tc during radioactive decays with principal radiation γ-ray, having specific γ-ray constant of 0.19 mGy per MBq-h-1at-1 cm. Figure 9.3 shows a cross-sectional view of the ⁹⁰Mo–^99mTc generator.

Radionuclides for the use in nuclear medicine are also produced in nuclear reactor by the process of fission, neutron capture, or transmutation, for example, ¹³¹I, ¹³³Xe, and ⁹⁹Mo. Table 9.2 shows the parent and daughter nuclei and their applications, and the isotopes used in nuclear medicine are given in Table 9.3. Atomic nuclei with the same number of protons, but with different numbers of neutrons, are called isotopes. Isotopes are identified as stable, when the protons and the neutrons in the atom can coexist in a state of peaceful tranquility. On the other hand, the isotopes that spontaneously emit radiation are called radioisotopes. The relative abundance of three isotopes of potassium (K) (³⁹K, ⁴⁰K, and ⁴¹K, have 19 protons, and (39–19), (40–19), and (41–19) neutrons) are constant, regardless of the source. Even the human body contains almost 150–200 g of potassium (K) of which 20–25 mg exists as a radioisotope (⁴⁰K). The other natural radioisotopes are carbon (¹⁴C) and hydrogen (³H, tritium) that result from the nuclear reactions of the atmospheric nitrogen (N). During our lifetime, we absorb and excrete ¹⁴C, and as a result, ¹⁴C levels in our tissues gradually increases to an equilibrium level and in course of time it decays due to its radioactive nature. But the half-life of ¹⁴C is 5,730 years, so the effect of decay is not much noticeable during our lifetime.

A revolution in radiotherapy has been possible for the reactor-based radionuclides, which are β-emitters such as ¹⁵³ Sm, ¹⁸⁶Re, ¹⁶⁶Ho, ¹⁷⁷Lu, and ¹⁰⁵Rh. These radionuclides are used in more sophisticated radioactive targets including radioactive intra-arterial microspheres, chemically guided bone agents, labeled monoclonal antibodies, and isotopically tagged polypeptide receptor-binding agents [12]. Figure 9.4 shows the picture of the inside of a nuclear reactor.

Ernest Lawrence in Berkeley, CA, reported the invention of cyclotron in 1934 and recognized the possibilities of the machine to produce artificial radioisotopes for the application in medicine. In 1937, Joseph Hamilton was the first to use the radioisotopes to study circulatory physiology [13]. The cyclotron accelerates charged particles such as hydrogen nuclei (protons) and heavy hydrogen nuclei (deuterons) to high energies. The molecules of deuterium at the center of the cyclotron are bombarded with electrons whose energy is high enough to produce positive ions during collisions.

Figure 9.5 shows the schematic of a cyclotron. D₁ and D₂ are the two dees made of copper sheet to which a high-frequency oscillator applies the accelerating voltage. The direction of the potential difference across the gap between the dees is made to change signs some millions of times per second. The dees are immersed in a magnetic field produced by a large electromagnet, and the space where the ions will move is evacuated to avoid collisions between ions. Table 9.4 shows some of the radioisotopes produced in cyclotron.

In external beam therapy (EBT), high energetic X-ray is administered to the location of the affected cells. The beam is generated outside the patient’s body usually by either a linear accelerator (LINC), orthovoltage X–ray machines, Cobalt–60 machines, proton beam machines, or neutron beam machines. In EBT no radioactive sources are placed inside the patient’s body. EBT can be successfully applied to treat any of the following diseases such as (1) breast cancer, (2) colorectal cancer, (3) head and neck cancer, (4) lung cancer, and (5) prostate cancer as well as many other cancerous cells inside a specific area of the body.

It is a form of external beam radiation treatment that uses protons rather than X-rays to treat certain types of cancer and other diseases. The physical characteristics of the proton therapy beam allow doctors to more effectively reduce the radiation dose close to nearby healthy tissues.

It is a specialized form of external radiation, which consists of neutrons instead of X-rays. Neutron beam therapy is a powerful tool, which is used to treat certain types of tumors that are radiation resistant, meaning that they are difficult to kill by using ordinary X-ray or proton beam therapy. As a matter of fact, neutrons have a greater biological impact on cells than other types of radiation.

LINC is a device mostly used for external beam radiation treatments for cancer patients [19]. In linear accelerator (LINC), electrons are accelerated by microwave technology similar to that used in radar. The waveguide then allows these electrons to collide with a heavy metal target. A portion of these X-rays coming out of the accelerator (called gantry) are collected and shaped into a narrow beam. The beam is usually rotated around the affected area of the cancerous cells of the body (Fig. 9.6).

The safety of the patient is very important during treatment, and the radiotherapist should continuously monitor the patient through a closed-circuit television monitor [20]. The development of a compact and fully digital LINC provides beam accuracy, treatment automation, and patient comfort—translating maximum radiation dose to the tumor, minimum dose to the surrounding tissue, and less time on table for the patients. Modern radiation machines have internal checking systems to provide further safety so that the machine will not turn on until all the treatment requirements are met.

The Leksell Gamma Knife is a neurosurgical device used to treat mostly brain tumors with radiation therapy. The device was invented by Lars Leksell, a Swedish neurosurgeon, in 1967 at the Karolinska Institute in Sweden. The procedure involves a highly targeted radiation source, which is focused precisely on the target from many different directions, and it has brought a revolutionary type of surgery in the field of nuclear medicine. The individual radiation beam is weak enough to harm the brain tissue it passes through. The beams of the gamma-ray radiation called blades are programed to target the lesion at the point where they intersect. The exposure session is generally brief and precise. Thus, the Gamma Knife is able to cut deep into the brain without using a scalpel at all.

Gamma Knife surgery is preferred to noninvasive (non-incision) surgery for brain tumors, arteriovenous malformations, and brain dysfunction like neuralgia [21]. It is an alternative nonsurgical operation for many patients for whom the traditional surgery is not an option. The greatest advantage of the Gamma Knife technology is that it allows treatment of inoperable lesions. The risks of Gamma Knife radiosurgery treatment include but are not limited to radiation necrosis, secondary malignancy head frame, paralysis, and death.

Figure 9.7 shows the picture of a Gamma Knife setup showing in details of the machine with the radiation source which can be focused from all directions. The setup also includes computerized data from imaging tests, to pinpoint areas within the brain and destroy them using multiple beams of gamma radiation [22]. Cumulative effect of the gamma rays from all directions produces a high dose of radiation at the exact site of the lesion, without damaging the healthy cells.

The proton beam therapy or radiosurgery has properties different from the radiation used by Gamma Knife and LINAC machines. Proton beams deliver almost all their radiation at a set distance from the radiation source, rather than gradually releasing the energy as the beam travels. This difference eliminates the need for multiple beams from different directions as we have seen in Gamma Knife operation. To improve precision, a head frame is used and metallic beads are also inserted under the skin to help the computer triangulate tumor volume. Sometimes, the instrument might have the facility to rotate the body so that the proton beam can be focused on the tumor from different angles. The main drawback with the process is that it required a highly specialized particle accelerator called synchrocyclotron, which made the processing costly [23].

Proton radiation therapy is considered as one of the most precise forms of noninvasive image-guided cancer therapy [24]. It is based on the well-defined range of protons in material, with low entrance dose and a maximum (Bragg peak) and a rapid distal dose falloff, providing better sporting of healthy tissue and allowing higher tumor doses than conventional radiation therapy with photons [25, 26].

Stereotactic radiosurgery (SRS) is a nonsurgical procedure that applies radiation therapy in a highly precise form to treat brain tumors and other abnormalities of the brain. The radiosurgery in SRS has such a dramatic effect in the target zone that the changes are considered as surgical [27]. The treatment involves the delivery of a single high dose or smaller multiple doses of radiation from an external source such as (a) linear accelerator or cyclotron, (b) Gamma Knife, and (c) proton beam. The SRS does not remove the tumor; instead, it destroys the DNA of tumor cells. It provides an external frame of reference for the subsequent radiation treatment planning. The linear accelerator, the cobalt source machines, and proton radiosurgeries are three different types of machines generally used in SRS.