**4. Vascular disruption using internal radiation-generating devices**

Vascular disruption can also be achieved using internal radiation-generating devices. These devices meet the desired characteristics to maximize dose to the tumor's vascular walls while minimizing the dose to healthy tissue. For a tissue volume irradiated by a beam of ions of a given energy, the absorbed dose (D) as a function of penetration distance into tissue is given by Eqs. (4) and (5). Arteriole vascular disruption is outlined for beams of protons, alpha particles, and 12C, 20Ne, and 40Ca ions. All beams were assumed to be fully ionized (e.g., 12C ions have a +6 e charge).

The photon absorbed dose is derived from Eq. (6). Because higher energy photons have poor dose localization, low-energy photons are investigated as a possible vascular disruption agent.

#### **4.1. Internal radiation-generating device results and discussion**

The base case considered in this chapter is the 20 μm arteriole wall thickness. With this emphasis, the dose delivered to the arteriole wall and blood vessel wall thicknesses ≤100 μm [17] is calculated. The target dose, which is about of 100 Gy, is sufficient to disrupt the vessel wall. Dose delivery has not been optimized, and ion fluences to reach the 100 Gy dose level are 5 × 109 , 5 × 108 , 1 × 108 , 5 × 107 , and 1 × 107 ions/cm2 for protons, alpha particles, 12C, 20Ne, and 40Ca, respectively. 1 × 1010 photons are utilized in the calculations using Eq. (6).

In subsequent absorbed dose calculations, the internal radiation-generating device is assumed to reside at the inner arteriole wall. **Table 2** summarizes the calculations for photons, protons, alpha particles, and 12C, 20Ne, and 40Ca ions and compares these results with betaemitting nuclides currently used in therapy applications. To further illustrate the internal radiation-generating device concept, **Figure 4** illustrates the 12C absorbed dose profiles for blood vessel wall depths ≤100 μm. The 12C energies included in **Figure 4** are 10, 20, 25, 30, 40, and 50 MeV. Water is assumed to be the medium comprising the vessel wall.

Radiotherapy Dose Optimization in Target Tissues Using Internal Radiation-Generating Devices and Microspheres http://dx.doi.org/10.5772/67203 225


a Maximum beta energy.

*3.4.9. 210Po toxicity and patient safety*

224 Radiotherapy

effective dose of about 0.3 μSv.

have a +6 e charge).

are 5 × 109

, 5 × 108

, 1 × 108

the patient is not significant. For example, if 10<sup>6</sup>

210Po has a specific activity of 1.7 × 1014 Bq/g, and its inhalation (ingestion) effective dose coefficient (EDC) is 3.0 × 10−6 Sv/Bq (2.4 × 10−7 Sv/Bq) [39]. The intake pathway caused by MA leaching has not been evaluated. In view of the inhalation and ingestion EDCs, the leaching EDC is probably in the range of the established conventional intake pathway values. For an initial scooping assessment, the leaching EDC is approximately 10−6 Sv/Bq. Considering the proposed 0.3 Bq 210Po MA, complete 210Po leaching from a single microsphere produces to an

The effective dose from complete MA leakage is mitigated if the microspheres have good retention characteristics. With good 210Po retention characteristics, the radiological hazard to

Vascular disruption can also be achieved using internal radiation-generating devices. These devices meet the desired characteristics to maximize dose to the tumor's vascular walls while minimizing the dose to healthy tissue. For a tissue volume irradiated by a beam of ions of a given energy, the absorbed dose (D) as a function of penetration distance into tissue is given by Eqs. (4) and (5). Arteriole vascular disruption is outlined for beams of protons, alpha particles, and 12C, 20Ne, and 40Ca ions. All beams were assumed to be fully ionized (e.g., 12C ions

The photon absorbed dose is derived from Eq. (6). Because higher energy photons have poor dose localization, low-energy photons are investigated as a possible vascular disruption agent.

The base case considered in this chapter is the 20 μm arteriole wall thickness. With this emphasis, the dose delivered to the arteriole wall and blood vessel wall thicknesses ≤100 μm [17] is calculated. The target dose, which is about of 100 Gy, is sufficient to disrupt the vessel wall. Dose delivery has not been optimized, and ion fluences to reach the 100 Gy dose level

In subsequent absorbed dose calculations, the internal radiation-generating device is assumed to reside at the inner arteriole wall. **Table 2** summarizes the calculations for photons, protons, alpha particles, and 12C, 20Ne, and 40Ca ions and compares these results with betaemitting nuclides currently used in therapy applications. To further illustrate the internal radiation-generating device concept, **Figure 4** illustrates the 12C absorbed dose profiles for blood vessel wall depths ≤100 μm. The 12C energies included in **Figure 4** are 10, 20, 25, 30, 40,

ions/cm2

, and 1 × 107

and 50 MeV. Water is assumed to be the medium comprising the vessel wall.

and 40Ca, respectively. 1 × 1010 photons are utilized in the calculations using Eq. (6).

**4.1. Internal radiation-generating device results and discussion**

, 5 × 107

retention of 90%, the patient's 50-year effective dose commitment is only 30 mSv.

**4. Vascular disruption using internal radiation-generating devices**

0.3 Bq MAs were administered with a 210Po

for protons, alpha particles, 12C, 20Ne,

b Internal radiation-generating device (IRGD).

c The dose decreases by a factor of about 103 over the listed depths.

dThe dose decreases by a factor of about 104 over the listed depths.

**Table 2.** Dose localization for candidate radionuclides and radiation types.

**Figure 4.** Absorbed dose profiles for 12C ions in water. The absorbed dose curves peak at a greater depth with increasing 12C ion energy. The total ion fluence for all energies is 1.0 × 10<sup>8</sup> 12C ions/cm2 . The ions are delivered by an internal radiation-generating device.

Dose localization within an arteriole wall could be achieved using 1.0–1.5 MeV proton beams. Alpha particles with energies below 3 MeV will not penetrate the arteriole wall. The arteriole wall is disrupted, with minimal dose to surrounding tissue, by alpha particles in the 4–5 MeV energy range. Sufficient absorbed dose to disrupt vessels with wall thicknesses between 20 and 100 μm can be delivered by alpha particles having energies below 8 MeV.

12C ions with energies below about 20 MeV do not penetrate the arteriole wall, and 20–50 MeV ions will deposit sufficient energy into a range of vessel wall thicknesses in the 20–100 μm range to produce vascular disruption. Selective arteriole wall disruption is achieved using 25–30 MeV 12C ions. However, the generation of 12C, 20Ne, and 40Ca ions is a more significant technical challenge than producing lighter ions in a first generation IRGD.

20Ne ions below 30 MeV do not penetrate the arteriole wall. 20Ne ions in the range of 50–110 MeV will be sufficient to reach the range of vessel wall thicknesses addressed in this chapter. Arteriole wall disruption with minimal dose to surrounding tissue is achieved using 50–70 MeV 20Ne ions. In a similar manner, 40Ca ions require 150–200 MeV to selectively disrupt the arteriole wall and 100–300 MeV 40Ca ions penetrate vessel wall thicknesses of 10–75 μm.

**Table 2** illustrates that photon energies in the range of 15–50 keV can deposit the requisite absorbed dose to disrupt an arteriole wall. Significant dose is also deposited in the 20–100 μm range by the 15–50 keV photons. However, protons and 4 He, 12C, 20Ne, and 40Ca ions achieve better dose localization.

Internal radiation-generating devices can also be developed to emit low-energy electrons. Electrons present a concern because their bremsstrahlung radiation can irradiate healthy tissue beyond the target volume. However, low-energy electrons preferentially irradiate the arteriole wall with minimal bremsstrahlung. **Table 3** summarizes the range and bremsstrahlung production for 20–85 keV electrons impinging on the arteriole wall.


**Table 3.** Vascular disruption by low-energy electrons from an internal radiation-generating device.

The results summarized in **Table 3** suggest that 35–40 keV electrons also offer the potential to selectively disrupt an arteriole servicing a tumor. Dose localization is achieved with minimal bremsstrahlung production that permits vascular disruption without delivering absorbed dose to healthy tissue. **Table 3** also illustrates that electrons below 85 keV also selectively irradiate vessel wall thicknesses below 100 μm.
