**2.1.2 Radionuclides**

In contrast with the transport molecules, the choice of the radionuclides differs for the two types of nuclear medicine procedures: diagnosis and therapy.

**Radionuclide diagnosis principle**: The incorporated radiopharmaceutical product, localized at the interest zone emits gamma-rays, which cross the body and are detected by the gamma cameras, containing a detection system, based on the use of scintillation detectors and a network of photomultipliers. A bi-dimensional image, called scintigram, is obtained; if the computer tomography principle is applied, a 3D image appears. In principle it is necessary to use as much as possible of the emitted radiation for detection and to avoid the unnecessary irradiation of the body; the irradiation detriment is expressed in terms of committed effective dose per activity unit, *E/A*. For this reason, the choice of radionuclides is focussed on the use of radionuclides with short half life and emitting low energy and intensity electrons and abundant gamma-rays, not much absorbed inside the body, and situated in the optimal energy detection interval, 100 – 600 keV. Two types of diagnosis procedures are in use:


A radipharmaceutical (RPM) product contains a radionuclide in an adequate chemical form, the transporter, which conducts it towards the organ or tissue of interest, when it is administrated to the patient "in vivo" by ingestion, inhalation or intravenous injection. In the case of diagnosis the radionuclide is used as a "tracer", while in therapy it is employed due to the cytotoxic effect of the emitted ionizing radiations. The radiopharmaceuticals are presented

Various types of transporters are used, formulated such as to assure a maximum localization of the radiopharmaceutical in the zone of interest while exposing the neibouring area to minimum detriment (Kornyei.2008, Mikolajczak. 2008). The types of transporters are generally similar for both of nuclear medicine procedures, diagnosis and therapy; some


iii. Peptide Receptor Radionuclide, somatostatin analogous: Pentetroid-DTPA-111In,

In contrast with the transport molecules, the choice of the radionuclides differs for the two

**Radionuclide diagnosis principle**: The incorporated radiopharmaceutical product, localized at the interest zone emits gamma-rays, which cross the body and are detected by the gamma cameras, containing a detection system, based on the use of scintillation detectors and a network of photomultipliers. A bi-dimensional image, called scintigram, is obtained; if the computer tomography principle is applied, a 3D image appears. In principle it is necessary to use as much as possible of the emitted radiation for detection and to avoid the unnecessary irradiation of the body; the irradiation detriment is expressed in terms of committed effective dose per activity unit, *E/A*. For this reason, the choice of radionuclides is focussed on the use of radionuclides with short half life and emitting low energy and intensity electrons and abundant gamma-rays, not much absorbed inside the body, and situated in the optimal energy


as ingerable gelatin capsules (or solutions), injectable solutions and inhalation gases.


i. Monoclonal antibodies (mAb): 90Y-anti-CD20; 188Re-anti-VEGF

The detailed description of these compounds is outside the scope of the chapter.

detection interval, 100 – 600 keV. Two types of diagnosis procedures are in use:

procedures, like the iodine uptake in thyroidal investigations.

TOC-HYNIC-99mTc. 188Re-DOTA-Lan and 188Re-Lan.

types of nuclear medicine procedures: diagnosis and therapy.

**2. Radiopharmaceutical products and their characterization by** 

**measurements** 

**2.1.1 Transporters** 

**2.1 Types of radiopharmaceutical products** 

formulations are presented as follows:


**2.1.2 Radionuclides** 

Na99mTcO4, 131INa, 89SrCl2, Na186,188ReO4 - Simple gas molecules: 11CO2, 15O2, 81mKr - Labeled organic molecules: 18F-DG; 67Ga-cytrate


ii. Meta Iodo Benzil Guanidine (MIBG)-131I


Table 1 presents a list of radionuclides used for the production of radiopharmaceuticals, in terms of production mode, nuclear decay data and *E/A*. Referring the *E/A* value, it is strongly dependent on the type of radiopharmaceutical, diagnostic procedure and the age of the patient; only for a rough information, the comparative dose values due to the ingestion of radionuclides by the adult public (ICRP 1996c) are given, in order to emphasize the strong dependence of the dose on the characteristics of the nuclear decay scheme.

The values of *E/A* from Table 1 are based on the Medical Internal Radiation Dose (MIRD) model, while at present time the calculation models use the "voxel phantom", defined in international documents as *"a computational anthropomorphic phantom based on medical tomographic images where the anatomy is described by small three dimensional volume elements (voxels) specifying the density and the atomic composition of the various organs and tissues of the human body"*. A special attention is paid to the radionuclide 99mTc, used nowadays in about 80% of the world diagnosis procedures. Its widespread use is due to several properties:


**Radionuclide (targeted) therapy principle**. The incorporated radiopharmaceutical is localized in the biological formation to be destroyed by irradiation. In this case, the entire energy of particles must be transferred to the matter. Consequently, low range radiations, such as: alpha particles and electrons - beta radiation, Auger and conversion electrons, are useful. This is the reason for which alpha, strong beta with high energy, electron capture and conversion decaying radionuclides are used. Lately a special attention is given to the beta-gamma triangular decay scheme radionuclides, with strong beta and weak gamma – ray energies and intensities, due to the ability to be monitored by a gamma camera during the treatment procedure. The half life can be from hours up to tens of days, in order to assure the prescribed dose to the biological formation to be destroyed. The choice of the radionuclides takes into account their chemical properties, as well as their radiations range in the tissue, which must be comparable with the dimensions of the biological formation to be destroyed. Table 2 presents a list of therapeutical radionuclides, with their modes of production, nuclear decay parameters and the tissue range.

Role of the Radionuclide Metrology in Nuclear Medicine 141

45.6 min α

Bi-212 60.54 min

β

α

β

Auger K

conversion electrons

14.28 d β Max 1710,

2.67 d β Max 2284,

50.65 d β Max 1492,

8.023 d β Max

1.956 d β Max

6.734 d β Max

3.775 d β Max

59.90 d Auger L

13.6d Internal

radiations

7.21 h α 5868-7448;

Energy, keV; Intensity

100%

5869; 2%

987-1426; 97%

6050-6090 ; 35.8% 1527-2250 ; 64.2%

3.7; 79.3%

22.7 - 34.5; 33.9%

127 keV 152 keV

mean 695.5; 100%

mean 939; 100%

mean 584; 100%

338-605, mean 97-192 ; 100%

634-807 , mean 200-263 ;100%

175.8-497.1, mean 47-149 ;100%

939.4-1077, mean

309-362; 93.1%

Tissue range Max./Mean

80 μm

70 μm

2.5 mm

80 μm

4.0 mm

Tens of nm

about 47μm

210 μm 290 μm

9.8 mm/ 2.8 mm

12 mm/ 4.0 mm

8 mm/ 2.5 mm

4mm/ 0.8 mm

5 mm/ 1.2 mm

1.6 mm/ 0.7 mm

5.0mm/ 1.7 mm

Obtaining Half life Type of

Type Radio

Alpha emitters

Electron capture (EC) radio nuclides

Pure beta emitters

Beta gamma emitters nuclide

213Bi 225Ac (10 d) generator

212Bi 212Pb (10.64h) generator

211At Cyclotrone 209Bi (α,2n)211At

225Ac is in 237Np decay chain or cyclotrone: 226Ra(p,2n)225Ac

212Pb is in natural 232Th chain, or Cyclotrone: 210Po (t, p)212Bi

125I NR: 124Xe (n, γ) 125Xe, EC, 125I

117mSn NR: 116Sn(n, γ)117mSn

32P NR: 32S(n,p)32P

90Y NR: 89Y(n,γ)90Y;

89Sr NR: 88Sr (n,γ)89Sr or 235U fission

131I NR: 130Te(n, γ)131Te, <sup>β</sup>

153Sm NR: 152Sm(n, γ) 153Sm

177Lu NR: 176Lu (n, γ)177Lu or:

186Re\*\* NR:

decay, 131I or 235U fission

176Yb(n, γ)177Yb, β decay, 177Lu

185Re(n, γ)186Re

 or 235U fission: Generator: 90Sr (28.15 y):



Table 1. The most used radionuclides for diagnosis. Monographie BIPM-5 (Bé et al. 2004), ICRP1996c (1996).

8.02 d β\_ γ

13.2 h e

3.26 d e

3.04 d e

6.007 h e

2.80 d e

12.8 s e

110 min β<sup>+</sup>

20.4 min β<sup>+</sup>

67.7 min β<sup>+</sup>

12.70 h β<sup>±</sup>

NR\* = Nuclear Reactor. In the future, most of NR produced radionuclides is expected to be obtained from high neutron flux sources, based on the use of a proton accelerator and the emission of neutrons by the accelerated protons reaction with a mercury target. 99Mo can be produced also at a linear

Table 1. The most used radionuclides for diagnosis. Monographie BIPM-5 (Bé et al. 2004),

X γ

γ

X Y

X γ

X γ

X γ

γ<sup>±</sup>

γ<sup>±</sup>

γ<sup>±</sup>

γ<sup>±</sup>

Obtaining Half life Emitted radiations *E/A*,

Type Energy, keV Intensity

248-606 max 364.5

127-158 27-32 159

84-93 91 -393

16-153 12-82 167.5

120-138 18.3-20.7 140.5

145-219 23-27 171.3 245.4

176 -188 12.6-14.1 190.3

634 max, tissue range 2mm 511

960 max 511

1899 max 511

653 max 511

%

100 81.6

3.36 85.6 83.3

35 87

51.8 140 10

11 7.6 89

13.6 3.2 90.6 94

32.1 16.8 67.1

96.9

194

100 200

88 178

56.9 35.7 *mSv/MBq* adults, ingestion

22

0.22

0.19

0.095

0.022 / diagnostic 0.005-0.029 (Toohey & Stabin. 1996)

0.29

0.00004 inhallation

0.049

0.024

0.10

0.12

Type of Diagnostic Radio nuclide

SPET 131I NR\*:

123I Cyclotrone:

67Ga Cyclotrone:

201Tl Cyclotrone:

111In Cyclotrone:

81mKr Cyclotrone:

11C Cyclotrone:

PET 18F Cyclotrone:

accelerator: <sup>100</sup> <sup>99</sup> Mo( , ) Mo γ*n*

ICRP1996c (1996).

111Cd(p,n)111In

79Br(α,2n)81Rb

20Ne(d,α)18F

14N(p, α)11C

64Cu NR:63Cu(n,γ)64Cu Cyclotrone: 64Zn(d,2p)64Cu

68Ga 68Ge generator (270.83 d) Cyclotrone: 66Zn(α,2n)68Ge

99mTc NR:

123Te(p,n)123I

67Zn(p,n)67Ga

130Te (n,γ)131Te, β decay, 131I, or 235U fission

203Ta(d,4n)201Pb. E.C.201Tl

99Mo generator (2.75 d) 98Mo(n, γ)99Mo or 235U fission

81Rb generator (4.25 h)

18O(p,n)18F; 16O(α,pn)18F;


Role of the Radionuclide Metrology in Nuclear Medicine 143

(*1996), para.II.19,* such as follows: *"the calibration of sources used for medical exposure shall be traceable to a Standard dosimetry laboratory*" and *"unsealed sources for nuclear medicine procedures shall be calibrated in terms of activity of the radiopharmaceutical to be administrated, the activity being determined and recorded at the time of administration"*. The conclusion of these assertions is that the activity must be precisely measured and the metrological traceability up to the

In radiopharmacy and nuclear medicine units, the activity is usually determined using Radionuclide Activity Calibrators, or Dose Calibrators. They contain a reentrant (well type) ionization chamber under pressure, connected to an electrometric system. The manufacturers perform the calibration of the equipment in terms of calibration factors, introduced in dial settings, established for a list of the most used medical radionuclides. The calibrations are performed using sets of standard solutions, provided by the radionuclide metrology laboratories or by commercial producers, having metrological traceability to a primary activity standard declared. Usually, these factors are determined for various types of recipients used in hospitals, such as: P6 or Schott 10-R vials, syringes, gelatin iodide

The pharmacopoeias impose the uncertainty limits in the measurement of activity, as: <5% for therapy and <10% for dignosis. The activity is measured in radiopharmacy, but it must be measured also in the hospital, as several operations, such as portioning, administration with a syringe, are carried by the involved staff**.** Due to the crucial importance of these measuremens, the radionuclide calibrator precision in the calibration and maintenance of its corresponding technical condition, together with the correct method of activity measurement in the nuclear medicine units are matters of concern at international level. The IAEA initiated a program aimed to improve and harmonize the quality of activity measurements. In November 2002 a group of consultants had a meeting in the IAEA Vienna headquarters, giving advice on the Methodology of Radioactivity Standardization. The Coordinated Research Project (CRP) codified as: E2.10.05, entitled: *"Harmonization of quality practices for nuclear medicine radioactivity measurements*" was started in 2004. Following the recommendations of the first meeting, a second consultants meeting was held and recommended to develop a set of procedures in the form of a draft Code of Practice in radioactivity measurement. Among other results of the CRP deployment, the elaboration of the above named document TRS454: *Quality Assurance for Radioactivity Measurement in Nuclear Medicine* was very important. The document presents in detail (Table 4, page 69) the types of tests and acceptance criteria for radionuclide activity calibrators to be performed upon the initial acceptance in the unit or after repair, daily checks in the hospital, monthly and annually. As for accuracy of measurement, an upper limit of 5% is imposed. In this respect, a radionuclide metrology laboratory is the entity providing assurance of metrological traceability chain directly, by providing standards, by performing calibrations and by organizing proficiency tests among the personnel doing measurements in radiopharmacy, in the control authorities, at the calibrators' producers and the nuclear medicine staff.The requirement of accuracy in the metrology laboratory is 2%. It can be primary activity standard, or a secondary one, metrologically traceable to a primary activity standard, disposing of a calibrated reentrant ionisation chamber, such as described by

**(ii) Specific activity, expressed in units, Bq g-1 of solid mass**. It defines the activity of the mass unit of the chemical element or solid compound and determines the capacity of

primary level must be assured.

capsules, etc.

(Schrader, 1997).


\*\*) When a natural Rhenium target is irradiated, a mixture 186Re+188Re is obtained. It can be used in this composition, for the short time irradiation of the external part of large dimension tumors by 188Re and for the long time irradiation of their cores by 186Re. Otherwise, after a week period 188Re decays and almost pure 186Re is obtained. 186Re and 188Re are very important for the obtaining of therapy pharmaceuticals, due to their similar chemical behavior (VII b group) with 99mTc, very extensively studied.

Table 2. Radionuclides used for therapy radiopharmaceuticals.
