Halperin7e_CH29

655

C H A P T E R 2 9  Radioimmunotherapy and Unsealed Radionuclide Therapy

RIT, the dose rate is 1,000-fold lower; therefore, the quadratic portion of the curve will have a much lower impact on survival because many SSBs, considered sublethal damage, will be repaired during the more lengthy delivery of LDR radiation. This will result in a “small” or absent observable shoulder and flattening of the cell survival curve. Thus, when estimating cell survival for RIT, α alone will define the radiosensitivity of the tumor (blue line in Fig. 29.3). Considering dose rate alone, RIT is approximately 20% less effective than HDR EBRT. Regardless, RIT does appear to be effective. This phenome- non can be attributed to many radiobiologic processes that appear to cause greater than predicted rates of apoptosis. These processes include low-dose/dose rate apoptosis, low- dose hyperradiosensitivity-increased radioresistance, inverse dose rate effect (G 2 synchronization), radiation-induced bio- logic bystander effect, and the crossfire effect. 30 The use of high-LET radiation, in the form of alpha particles or Auger electrons, will further increase cell kill. Various radionuclides have been proposed for the use in RIT (Table 29.4), and their physical properties have been extensively reviewed in the nuclear medicine literature. They can be grouped into three basic categories depending on the type of emitted particulate radiation. Radionuclides that emit high-energy electrons are referred to as β -emitters. These electrons have maximum path lengths in tissue from 0.6 to 12.0 mm. This translates into a range of approximately 60 to 1,100 cell diameters. The most commonly used β -emitters for RIT are yttrium 90 [ 90 Y], iodine 131 [ 131 I], and lutetium 177 [ 177 Lu]. The maximum range of electrons in tissue for 90 Y and 131 I is 12 and 2 mm, respectively. It should be noted, however, that 90% of the electron energy is deposited over 5.2 mm for 90 Y and 0.7 mm for 131 I. This range of 90% energy deposition is referred to as the R 90 . The most commonly used α -emitters for RIT are 211 At and 225 Ac. An α -particle is a helium nucleus that has a maximum range in tissue of 55 to 100 μ m (5 to 10

Section II

DSB, and the cell survival versus absorbed dose is a pure exponential function: S = e − α D where S is the surviving cell fraction and D is the mean absorbed dose. Ionizing irradiation may also cause nonlethal single-strand breaks (SSBs). If these events accumulate, they may become lethal. The constant, β , is used to describe this phenomenon and represents the more distant, “linear” portion of the cell survival curve. The linear- quadratic (LQ) model combines the two processes into a con- tinuously bending curve: S e D D = − − a b 2 The shoulder on the cell survival curve is typically observed when HDR radiation is employed (green line in Fig. 29.3). In FIGURE 29.3.  Cell survival curves following treatment with radiotherapy. The blue curve represents low–dose rate radiotherapy; the green curve represents high–dose rate radiotherapy. Increasing LET is represented by the red line (alpha particle radiation; RBE = 5) and gold line (Auger radiation; RBE = 7 to 9). (Adapted from Bernhardt P, Speer TW. Modeling the systemic cure with targeted radionuclide therapy. In: Speer TW, ed. Targeted radionuclide therapy . Philadelphia: Lippincott Williams & Wilkins, 2011:265. With permission.)

TABLE 29.4  POTENTIAL RADIONUCLIDES FOR RADIOIMMUNOTHERAPY Radionuclide Physical Half-Life E ave (MeV) a

Maximum Range in Tissue LET (keV/ μ m)

Approximate Cell Diameters

β -Particle

Beta-emitters Yttrium 90 Iodine 131 Lutetium 177 Rhenium 186 Rhenium 188 Phosphorus 32 Phosphorus 33 Holmium-166 α - Emitters Bismuth-213 Bismuth-212 Astatine-211 Actinium-225 Terbium-149 Copper 67

0.2

2.7 d 8.0 d 6.7 d 3.7 d

2.19 0.28 0.15 0.36 0.80 0.18 0.70 0.08 1.86 5.87 6.09 5.87 5.83 3.97

12.0 mm 2.0 mm 1.5 mm 3.6 mm 11.0 mm 2.8 mm 7.6 mm 0.6 mm 8.4 mm 55–60 μ m 60–70 μ m 55–60 μ m 60–90 μ m 30–60 μ m 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm 2–500 nm

400–1,100

10–230 4–180 15–360

17.0 h 2.6 d 14.3 d 25.3 d

200–1,000

5–210

760

60

1.1 d

840

α - Particle

80

45.7 min 60.6 min

5–6 6–7 5–6 5–8 3–6

7.2 h 9.92 d 4.12 h

Low-Energy Electron Emitters (Auger)

Low-Energy Electron

4–26

Iodine 125 Iodine 123 Gallium 67 Indium 111

60.1 d 0.55 d 3.26 d 2.80 d 6.01 h 4.33 d 4.02 d 2.80 d 38.9 h 72.9 h 57.0 h 4.4 h 27.7 d

0.030 0.030 0.009 0.026 0.018 0.053 0.063 0.072 0.028 0.078 0.012 0.013 0.005

<1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1 <1

Technetium 99m Platinum-193m Platinum-195m Platinum-191 Antimony-119 Thallium 201 Bromine-77 Bromine-80m Chromium 51

a When appropriate. Data were obtained from Eckerman KF, Endo A. eds. MIRD Radionuclide Data and Decay Schemes . 2nd ed. SNM MIRD Committee, 2008. E max , maximum energy; LET, linear energy transfer.