Radiopharmaceuticals For Therapy

Radioisotopes used in therapy require certain characteristics that differ from those of diagnostic radioisotopes. Radionuclides used in therapy are predominantly beta or alpha emitters (Table 1). Pure particle emitters without any gamma component do not require special radiation safety precautions permitting out-patient treatment. Presence of gamma emission is helpful in imaging and studying the biodistribution of a particular radiopharmaceutical, not only at the time of drug development but also for estimating patient-specific radiation absorbed dose. In the absence of gamma emission, internal dosimetry for alpha or beta emitters has been attempted using surrogate isotopes, for example, indium-111 (111In) for yttrium-90 (90Y) (1) although arguments counter to this application have been put forth. Emitters of Auger electrons, for example, In-111 have also been introduced for treatment purposes (2).

A number of radioisotopes are used as their salts, for example, 131I sodium iodide and 89Sr strontium chloride, while many others have to be incorporated into compounds of biological interest to make them stable and functional in vivo. These can be chemical compounds such as diphosphonate ethylene diamine tet-ramethylene phosphonate (EDTMP)—samarium- 153 (153Sm) EDTMP or biological compounds such as antibody—131I tositumomab. The resulting radiopharmaceutical

Table 1 Physical Characteristics of Commonly Used Radioisotopes in Therapy

Gamma energy

Beta Emax

Mean range

used for

Radionuclide

(MeV)

(mm)

imaging (keV)

Half-life (hr)

32P

1.71

1.85

342

64Cu

0.57 and 0.66

0.4

511

12.8

67Cu

0.57

0.27

92 and 185

62

90y

2.27

2.76

64

13Y

0.61

0.4

364

193

153Sm

0.8

0.53

103

47

177Lu

0.5

0.28

113, 208

162

186Re

1.07

0.92

137

89

188Re

2.12

2.43

155

17

165Dy

1.29

2.33?

225Ac

240

211At+

5.9 (alpha)

0.06

670

7.2

7.5 (e.c.)

0.08

212Bi

1.36 (beta)

0.09

727

1.0

213Bi

6.1 (alpha)

0.06

5.8 (alpha)

0.06

440

0.78

8.4 (alpha)

0.08

Abbreviations: P, phosphorus; Cu, copper; Y, yttrium; I, iodine; Sm, samarium; Lu, lutitium; Re, rhenium; Dy, dysprosium; Ac, actinium; At, astatine; Bi, bismuth.

Abbreviations: P, phosphorus; Cu, copper; Y, yttrium; I, iodine; Sm, samarium; Lu, lutitium; Re, rhenium; Dy, dysprosium; Ac, actinium; At, astatine; Bi, bismuth.

has the desired biodistribution and function of the drug moiety. The ultimate therapeutic function of a radioconjugate depends not only on the properties of the radioisotope but also on the biokinetic properties of the conjugate. These characteristics determine the global as well as local radiation absorbed doses for each combination.

Physical and effective half-life of the radioisotope should be paired to the drug half-life in the body. Radioisotopes with very short half-lives are often not desirable because of difficulties in availability, need for rapid labeling requirements. In spite of these drawbacks, short-lived isotopes, both alpha (212Bi and 213Bi) and beta emitters (67Cu), have been proposed and tried in the treatment of acute leukemia (3) as well as intracavitary applications (4).

Easy availability and production are attributes affecting the cost of production. Generator-produced isotopes are attractive particularly for use in centers that are remote from production facilities, for example, rhenium-186 (186Re). But cost might be a factor in their ready acceptance for routine clinical use. Simple, stable radiolabeling to biological compounds is one of the most important qualities for an ideal therapeutic isotope. Binding efficiency and stability of a radiolabeled compound results in optimal delivery of radiation in vivo. Additionally, there should not be any significant radiolysis of the compound after labeling, during storage (a potential problem when high specific activities are used in labeling), and shipment.

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