ASTATINE-211

BIBLIOGRAPHY TO SECTION 2.3

BASILE, D., et al., Excitation functions and production of arsenic radioisotopes for environmental toxicology and biomedical purposes, Int. J. Appl. Radiat. Isot. 32 (1981) 403–410.

DMITRIEV, P.P., MOLIN, G.A., The yields of As-73 and As-74 in nuclear reactions with protons, deuterons and alpha particles, Sov. At. Energy (Engl. Transl.) 41 (1976) 657–661.

HORIGUCHI, T., KUMAHORA, H., INOUE, H., YOSHIZAWA, Y., Excitation function of Ge(p, xnyp) reactions and production of ⁶⁸Ge, Int. J. Appl. Radiat. Isot. 34 (1983) 1531–1535.

LEVKOVSKIJ, V.N., in Activation Cross Sections for the Nuclides of Medium Mass Region (A = 40–100) with Medium Energy (E = 10–50 MeV) Protons and Alpha Particles: Experiment and Systematics, Inter-Vesi, Moscow (1991).

2.4. ASTATINE-211 Half-life: 7.2 h.

Uses

Because of the high linear energy transfer (LET) associated with alpha particles, alpha emitters have long been thought to have therapeutic potential (See representative articles in the bibliography to this section). Astatine-211, because of its alpha energy of 5.7 MeV, is a very attractive isotope for cancer therapy. It has been used to attach to antibodies, proteins, drugs and inorganic colloids. The main problem is getting the astatine to remain attached to the molecule under physiological conditions. It should be pointed out that there is a potential radionuclidic contaminant (²¹⁰At) that must be minimized because of its decay product (²¹⁰Po), which is a pure alpha emitter and chemically binds to the bone marrow.

Decay mode

Astatine-211 decays via electron capture (59%) and alpha emission (41%). The decay product of the electron capture, ²¹¹Po, decays by alpha emission (100%). Thus, every decay of ²¹¹At results in an alpha particle.

Alpha emission products of ²¹¹At

Alpha emission products of ²¹¹Po

Electron emission products of ²¹¹At

Photon emission products of ²¹¹At

Fraction Energy (MeV)

0.000045 5.1959

0.418 5.870

Fraction Energy (MeV)

0.00544 6.568

0.00557 6.892

0.989 7.450

Fraction Energy (MeV) Fraction Energy (MeV)

0.013462 0.059700 0.261490 0.008330

Fraction Energy (MeV) Fraction Energy (MeV)

0.000044 0.685160 0.127020 0.07686

0.002455 0.687000 0.197270 0.011100

0.095480 0.089800 0.212760 0.079290

2.4. ASTATINE-211

Photon emission products of ²¹¹Po

Decay scheme

The decay scheme of ²¹¹At is shown in Fig. 2.4.1.

Note that the daughter from the alpha decay of ²¹¹At is radioactive, ²⁰⁷Bi (t_½ = 32.2 a). However, because of the half-life differences, the photon intensities from ²⁰⁷Bi will be less than 10^–5 relative to the amount of ²¹¹At.

Excitation functions

The excitation functions for ²⁰⁹Bi(a, 2n)²¹¹At and ²⁰⁹Bi(a, 3n)²¹⁰At are shown in Figs 2.4.2 and 2.4.3, respectively.

Fraction Energy (MeV) Fraction Energy (MeV)

0.000032 0.328200 0.005380 0.897830

0.005219 0.897830 0.005380 0.569670

FIG. 2.4.1. Decay scheme of ²¹¹At.

20 30 40 50 60 70

FIG. 2.4.2. Excitation function for the ²⁰⁹Bi(a, 2n)²¹¹At reaction.

0 10 20 30 40 50 60 70

FIG. 2.4.3. Excitation function for the ²⁰⁹Bi(a, 3n)²¹⁰At reaction.

2.4. ASTATINE-211

Thick target yields of ²⁰⁹Bi(aa, 2n)²¹¹At

As can be seen from the excitation function, the yield of ²¹¹At is very sensitive to the bombarding energy; thus, a theoretical calculation is not warranted. The table below compiles some of the results in the literature, which show a fairly wide range. Each publication in the reference list to this section has details regarding the target backing, and whether an internal or external beam was used; thus, the reader is encouraged to consult the literature to learn the details from the respective authors in order to obtain a perspective.

Thick target yields for production of ²¹¹At

Target material

The target material of choice is high purity bismuth metal.

Target preparation

Just as in the yield variation, there is a fairly wide range of target preparation procedures. However, the consensus is that an aluminium backing is preferred because of its ease of handling and adequate thermal properties. It should be noted that bismuth has a relatively poor thermal conductivity and a low melting point.

Bismuth can be melted onto the backing, pressed or vacuum evaporated.

Because of the physical properties of bismuth, as thin a layer as possible is recommended. Thus, the target should be operated at a slant so as to take advantage of the increased target thickness while maintaining a thin profile.

The aluminium backing should be water cooled. It should be noted that copper has been tried, but with lower yields than those with aluminium.

Alpha energy (MeV) TT yield (mCi/mA·h) Reference

28 41 [2.4.1]

28–29 16.3 [2.4.2]

29.1 30 [2.4.3]

29.5 38 [2.4.4]

Target processing

The standard method for removing ²¹¹At from the bismuth target matrix is by dry distillation at 650°C in a quartz oven. A dry nitrogen, argon or oxygen carrier gas is used to carry the ²¹¹At out of the still. The distilled astatine is trapped in a polyetheretherketone® (PEEK) tubing cooled to –77°C with a mixture of ethanol and dry ice. The trapped astatine can be recovered with a small volume of organic solvent.

While there are reports of possible wet chemical methods being used to isolate astatine from bismuth targets, there are no publications with reliable results describing this approach.

Enriched materials recovery

Natural bismuth is monoisotopic ²⁰⁹Bi. There is no need to recover the target material.

Specifications

As indicated below, the major contaminant is ²¹⁰At/²¹⁰Po. Since there are no stable isotopes of astatine, the SA will approach the theoretical values. However, as in all radiochemical processes, there is always the necessity of removing or minimizing pseudo-carriers, which may be in the form of another halogen in this case.

The primary concern is the amount of ²¹⁰At/²¹⁰Po as a radionuclidic impurity, because its decay product (²¹⁰Po) is a pure alpha emitter and binds chemically to bone marrow. The level of impurity acceptable will have to be decided by the local authorities. However, Henriksen et al. [2.4.3] suggested that at 29.1 MeV the relative atomic content of ²¹⁰At at end of bombardment (EOB) is approximately 0.023%.

For assay purposes, the following table contains relevant decay properties for the 210 chain.

Decay properties of the 210 chain

Nuclide Half-life Decay mode Gamma energy (keV) Per cent

At-210 8.1 h EC 245.3 79.5

1181.4 99.4

1483.3 46.5

Po-210 138.4 d a 803 0.00121

Note: Table adapted from Ref. [2.4.5].

2.4. ASTATINE-211

REFERENCES TO SECTION 2.4

[2.4.1] LARSEN, R.H., WEILAND, B.W., ZALUTSKY, M.R., Evaluation of an internal cyclotron target for the production of ²¹¹At via the ²⁰⁹Bi(a, 2n)²¹¹At reaction, Appl. Radiat. Isot. 47 (1996) 135–143.

[2.4.2] SCHWARZ, U.P., et al., Preparation of ²¹¹At labeled humanized anti-tac using

211At produced in disposable internal and external bismuth targets, Nucl. Med.

Biol. 25 (1998) 89–93.

[2.4.3] HENRIKSEN, G., MESSELT, S., OLSEN, E., LARSEN, R.H., Optimisation of cyclotron production parameters for the ²⁰⁹Bi(a, 2n)²¹¹At reaction related to biomedical use of ²¹¹At, Appl. Radiat. Isot. 54 (2001) 829–834.

[2.4.4] LEBEDA, O., JIRAN, R., RÁLIŠ, J., ŠTURSA, J., A new internal target system for production of ²¹¹At on the cyclotron U-120M, Appl. Radiat. Isot. 63 (2005) 49–53.

[2.4.5] LARSEN, R.H., et al., Alpha-particle radiotherapy with ²¹¹At-labelled monodis-persed polymer particles, ²¹¹At-labelled IgG proteins, and free ²¹¹At in a murine intraperitoneal tumor model, Gynecol. Oncol. 57 (1995) 9–15.

BIBLIOGRAPHY TO SECTION 2.4

ANDERSSON, H., et al., Radioimmunotherapy of nude mice with intraperitoneally growing ovarian cancer xenograft utilizing ²¹¹At-labelled monoclonal antibody MOv18, Anticancer Res. 20 (2000) 459–462.

GROPPI, F., et al., Optimisation study of alpha-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes, Appl. Radiat. Isot. 63 (2005) 621–631.

HADELY, S.W., WILBUR, D.S., GRAY, M.A., ATCHER, R.W., Astatine-211 labeling of an antimelanoma antibody and its Fab fragment using N-succinimidyl p-Asatoben-zoate: Comparison in vivo with the p-[¹²⁵I]iodobenzoylconjugate, Bioconjug. Chem. 2 (1991) 171–179.

HERMANNE, A., et al., Experimental study of the cross-sections of alpha-particle induced reactions on ²⁰⁹Bi, Appl. Radiat. Isot. 63 (2005) 1–9.

INTERNATIONAL ATOMIC ENERGY AGENCY, Charged Particle Cross-section Database for Medical Radioisotope Production: Diagnostic Radioisotopes and Monitor Reactions, IAEA-TECDOC-1211, IAEA, Vienna (2001).

IMAM, S.K., Advancements in cancer therapy with alpha emitters: A review, Int. J.

Radiat. Oncol. Biol. Phys. 51 (2001) 271–278.

LAMBRECHT, R.M., MIRZADEH, S., Astatine-211 — Production, radiochemistry and nuclear data, J. Labelled Compd. Radiopharm. 21 (1985) 1288–1289.

LAMBRECHT, R.M., MIRZADEH, S., Cyclotron isotopes and radiopharmaceuticals XXXV: Astatine-211, Int. J. Appl. Radiat. Isot. 36 (1985) 443–450.

LARSEN, R.H., et al., ²¹¹At-labelling of polymer particles for radiotherapy: Synthesis, purification and stability, J. Labelled Compd. Radiopharm. 33 (1993) 977–986.

LINDEGREN, S., BÄCK, T., JENSEN, H.J., Dry-distillation of astatine-211 from irradiated bismuth targets: A time-saving procedure with high recovery yields, Appl.

Radiat. Isot. 55 (2001) 157–160.

PALM, S., et al., In vitro effects of free ²¹¹At, ²¹¹At-albumin, and ²¹¹At-monoclonal antibody compared to external photon irradiation for two human cancer cell lines, Anticancer Res. 20 (2000) 1005–1012.

RAMLER, W.J., WING, J., HENDERSON, D.J., HUIZENGA, J.R., Excitation functions of bismuth and lead, Phys. Rev. 114 (1959) 154–162.

UNITED STATES NATIONAL NUCLEAR DATA CENTER, http://www.nndc.bnl.gov/

VAIDYANATHAN, G., ZALUTSKY, M.R., Targeted therapy using alpha emitters, Phys. Med. Biol. 41 (1996) 1915–1931.

WILBUR, D.S., et al., Preparation of and evaluation of para-[²¹¹At]astatobenzoyl labeled anti-renal cell carcinoma antibody A6H F(ab0)2 in vivo distribution comparison with para-[¹²⁵I]iodobenzoyl labeled A6H F(ab0)2, Nucl. Med. Biol. 20 (1993) 917–927.

ZALUTSKY, M.R., et al., Radioimmunotherapy of neoplastic meningitis in rats using an a-particle-emitting immunoconjugate, Cancer Res. 54 (1994) 4719–4725.

2.5. BERYLLIUM-7