Unsealed Radioisotope Preparations Based on Cyclotron Irradiation

Charged particles (e. g., protons and deuterons) generated in cyclotrons may partici­pate in nuclear reactions, resulting in several new radionuclides used mainly for medical purposes. According to proton energy, the following cyclotron types are known:

Medical or “baby” cyclotrons installed on the site of the application of radionuclide with maximum proton energy of 10—12 MeV, suitable for producing very short-lived (T1/2 < 2 h) radionuclides (18F, 13N, 11C, 15O; see Table 8.4). These radionuclides are tracers for PET, and all except 18F are found in living organs as chemical elements. Thus, they have the advantage that no foreign atom is used for labeling the organ-specific molecule and atoms naturally present in living organs can be labeled with their PET radionuclides.

• In industrial cyclotrons with higher proton energy (30—40 MeV), radionuclides of longer half-lives used both as industrial and medical tracers (67Ga, 201Tl, 111In, 123I, and 81Rb) can be produced. The latter is the parent of the isotope generator 81Rb/81Kr, the daughter of which, as noble gas, is used for lung diagnostics.

• The main application of the very-high-energy cyclotrons (70—200 MeV) is tumor ther­apy. In addition, cyclotrons with a high current density are used for producing radionu­clides of a low-proton-absorption cross section (e. g., 103Pd).

Подпись: Y = N<^(1 Подпись: e~At) image411 Подпись: (8.25)

For cyclotron irradiation, the yield Y (Bq/pA • h) of the nuclear reaction can be calculated with the following formula:

where N is the number of target atoms in a given volume, Ф is the flux of the bom­barding particle, a is the cross section of the target element, E is the energy of the bombarding particle, and X is the thickness of the target. (This equation is another form of Eq. (6.9).)

Among cyclotron isotopes, the 18F radionuclide and its labeled compound, 18F-fluorodeoxyglucose (18FDG), has the most important and the highest utilization.

Today, the fluorination reaction following the target irradiation is a fully automated, computer-controlled process using “synthesis panels,” which carry out computed steps of the reaction without human intervention (see Table 8.16).

Among radionuclides with longer half-lives produced in industrial cyclotrons, 67Ga, 201Tl, and 123I have practical importance in medical applications. These

Table 8.16 Preparation of 18F-Labeled FDG

Nuclear parameters

Half-life: 1.7 h.

Decay mode and energy: в+ (keV) 650 and y (keV) 512.


Deoxyglucose labeled with fluor 18F is suitable for

detecting glucose consumption that cells use for energy supply. Tumor cells, for instance, consume glucose at an increased rate, so diagnosis of such cells is possible with FDG. In addition to this, it is also suitable for detecting certain myocardial disorders and inflammations.

Target material

Water enriched with 18O.

Target irradiation

In cyclotron, at 75 pA.

Primary nuclear reaction

18O(p, n)18F.

Nuclear reactions resulting in

During chemical synthesis following irradiation, only the

contaminating nuclides

target isotope is bound to the molecule to be labeled, so carrier-free product is produced.

Steps of the FDG synthesis

Separation of fluor from the irradiated target on ion — exchange resin. Transfer of 18F into the organic phase with crown-ether. Fluorination of the FDG precursor with nucleophyllic substitution. Hydrolysis of the protecting groups with acid or alkaline. Separation of 18FDG from the reaction mixture.

Product finishing

Dispensing to the ordered number of ampoules.

Radiochemical yield

Approximately 70%

Obtained activity

Approximately 3.7 X 1011 Bq 18F corresponding to 2.5 X 1011 Bq 18FDG.

Radiochemical purity


products—due to their longer half-lives—can be transported over longer distances. Nuclear reactions that serve to generate these radionuclides are:

66Zn (d, n)67Ga (8.26)

203Tl (p, 3n)201Pb, followed by 201Pb! 201Tl (в 2 decay) (8.27)

122Te (p, n)123I (8.28)

Some radionuclides produced in high-energy cyclotrons are important radionu­clide generators.

Irradiation: 69Ga(p, 2n)68Ge!68Ge/68Ga generator

Irradiation: 85Rb(p, 4n)82Sr ! 82Sr/82Rb generator

As daughter nuclides emit positrons, these generators are used for PET images.

Table 8.17 The Most Frequently Used Quality Control Methods for Open-Vessel
Radioactive Preparations

Tested Parameter Test Method

Подпись: Activity meter with ionization chamber Activity/mass (determination by calculation, e.g., with ion-selective electrode) Activity/volume (by calculation) Gamma and beta spectroscopy Thin-layer chromatography pH paper and pH electrode (potentiometric method) Measurement of the parent and daughter activities Measurement of the parent and daughter activities Innoculation onto a medium; incubation LAL (limulus amebocite lysate) test Activity

Specific activity

Radioactive concentration Radionuclide purity Radiochemical purity pH

Separation yield of the parent and daughter radionuclides (at generators)

Parent nuclide concentration (as contamination) in the separated daughter nuclide—called a parent breakthrough Sterility

Endotoxin content (pyrogenity)

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