**4. Setting up of the activity secondary standard systems**

#### **Realisation of the activity secondary standards.**

Such as presented in figure 1 and as pointed in the references TRS 454 (2006) and (Zimmerman & Judge. 2007), the practical realization of the metrological traceability chain is possible by using the activity secondary standards. They are transfer instruments of the activity unit from the primary to the lower order, working standards, for the end users, through standard (reference) products or calibration services. They consist of installations for the secondary (relative) standardization; their calibration is done with sources and solutions absolutely standardized with the primary standards. In the case of the primary laboratories they use their own primary standards. In the case of the secondary standard laboratories (SSL), the standards leave from another primary laboratory, the traceability route being declared. The practical work at IFIN-HH, RML was described in (Sahagia & Woods.2008).

#### **4.1 Secondary standards for high activity radiopharmaceutical solutions**

The secondary standard for high activity solutions is a reentrant (well type) ionization chamber, filled with an inert gas as nitrogen or argon, at high pressure, of a special construction, largely described by H. Schrader in Monographie BIPM-4 (1997), or a commercial radionuclide calibrator. It is calibrated with standard solutions absolutely standardized, from the radionuclides of interest. The ionization current, registered by the associated electrometric circuit, is due to the radiations entering in the sensitive volume of the chamber and ionizing the filling gas. This chamber is mainly used for the measurement

Management System (QMS) is monitored by the EURAMET, Technical Committee –

At the level of CIPM - MRA, the statement is practically applied by the use of the Annex C of the CIPM-MRA, Calibration and Measurement Capability files – CMCs. The approval and publication of CMCs for a NMI is the result of two types of evaluation components for the international recognition: (i) Approval of the international equivalence for primary and of the traceability for secondary standards; (ii) Implementation of the QMS and recognition by

i. *Approval of equivalence and traceability.* The NMI, member of one MRO, draws up the primary or secondary CMC files. The statement is compared with the KCDB for primary, or in our case EURAMET for secondary standards. After the inter MROs' peer

ii. *Implementation and approval of the QMS.* The EN/ISO/IEC 17025:2005, referential *"General requirements for the competence of testing and calibration laboratories"* is applied. A complete documentation and its implementation are presented at the annual meetings of the EURAMET, TC-Q. The technical experts monitor the documents and after the first approval, the QMS is annually reconfirmed. This is a prerequisite condition to maintain the CMCs in the published in Annex C of MRA. *Example, IFIN-HH, RML situation.* 34 CMC files, Radioactivity standards, passed the peer review process; the QMS was approved in 2007 and annually reviewed. All CMCs were approved by the JCRB in April 2008 and published in CIPM-MRA, Annex C. http://kcdb.bipm.org/

Such as presented in figure 1 and as pointed in the references TRS 454 (2006) and (Zimmerman & Judge. 2007), the practical realization of the metrological traceability chain is possible by using the activity secondary standards. They are transfer instruments of the activity unit from the primary to the lower order, working standards, for the end users, through standard (reference) products or calibration services. They consist of installations for the secondary (relative) standardization; their calibration is done with sources and solutions absolutely standardized with the primary standards. In the case of the primary laboratories they use their own primary standards. In the case of the secondary standard laboratories (SSL), the standards leave from another primary laboratory, the traceability route being declared. The practical work at IFIN-HH, RML was described in (Sahagia &

The secondary standard for high activity solutions is a reentrant (well type) ionization chamber, filled with an inert gas as nitrogen or argon, at high pressure, of a special construction, largely described by H. Schrader in Monographie BIPM-4 (1997), or a commercial radionuclide calibrator. It is calibrated with standard solutions absolutely standardized, from the radionuclides of interest. The ionization current, registered by the associated electrometric circuit, is due to the radiations entering in the sensitive volume of the chamber and ionizing the filling gas. This chamber is mainly used for the measurement

review process, they are submitted for the approval of the JCRB.

**4. Setting up of the activity secondary standard systems** 

**4.1 Secondary standards for high activity radiopharmaceutical solutions** 

Quality, TC-Q.

the MRO's, TC-Q.

AppendixC/default.asp

Woods.2008).

**Realisation of the activity secondary standards.**

of activity for gamma-ray, but also for strong beta-ray emitters, when the ionization current is produced by the bremsstrahlung radiations. Usually, the calibration factor is expressed in terms of absolute or relative efficiency, or in ionization current per activity unit, *pA MBq*-1. The calibration must be performed for several geometries of the recipients containing radioactive solution, or gelatin capsules in the case of iodine radioisotopes, as the calibration factor depends on the geometrical dimensions. For example, the IFIN-HH, RML well type ionization chamber is of the type CENTRONIC IG12/20A, filled with argon at a pressure of 2MPa (20Atm); its construction was first described in (Grigorescu et al. 2003). Recently, the old electrometric system was replaced with an electrometer Keithley E6517A. The validation of the calibration factors was done by several comparisons: (i) with the measurements performed at PTB-Braunschweig-Germany with PTB standard solutions; (ii) with the IFIN-HH, RML results obtained in international comparisons; (iii) respectively with the value of the KCRV (Sahagia et al. 2010). The calibration factors are determined for the radionuclides: 241Am, 57Co, 99mTc, 186Re, 188Re, 153Sm, 177Lu, 75Se, 169Yb, 131I, 133Ba, 51Cr, 192Ir, 134Cs, 137Cs, 54Mn, 65Zn, 60Co, 152Eu and for three geometries: (i) Solid sources; (ii) 131I gelatin capsules; (iii) Solutions of volumes: 2 mL (PTB), 3.6 mL (SIR-BIPM), 5 mL (P6 used for radiopharmaceuticals). From the above list one may notice that the calibration is assured for the majority of medical radionuclides. The determined calibration factors allow the measurement and certification of the radiopharmaceutical solutions or capsules to be used for: (a) the calibration of the radionuclide calibrators, including those belonging to the radiopharmaceutical unit from IFIN-HH, (b) to be distributed to the interested laboratories, or (c) to be used for organization of national comparisons. The chamber operation is in compliance with the QMS rules, established in agreement with the requirements of the EN ISO/IEC 17025:2005 and TRS 454 document. The calibration uncertainty is in all cased less than 2.0%.

### **4.2 High resolution spectrometric system**

In the field of nuclear medicine, spectrometric systems are used for the measurement of the radionuclide impurity level in radiopharmaceuticals (RPMs); in order to perform an adequate check of the requirements imposed to the RPMs, the system must have a high resolution, to allow the identification of the main radionuclide and impurities, and to be sensitive enough (to have a low background) in order to detect impurities content of the order of <0.1%, such as it is required for 99Mo content in 99mTc.

IFIN-HH, RML disposes of a system containing a high resolution HPGe detector: relative efficiency 29%; energy interval 35 *keV* – 3 *MeV*; resolution: 0.85 *keV* (122 *keV*) and 1.74 *keV*  (1.332 *MeV*) and a computer driven, software GAMMA VISION, V 6.01 spectrometric analyser. The specialized program GESPECOR (Sima & Arnold. 2002), for geometry, matrix and coincidence summation corrections is implemented. An efficient shield, consisting from: 10 cm old lead; 1 *mm* tin; 2 *mm* electrolytic cooper, assures a maximum integral background rate on the whole energy interval of 1.4 *s*-1. The system is calibrated in terms of energy and efficiency with standard sources, in various geometries from point sources up to volume recipients, prepared from standard solution absolutely standardized, by the coincidence method. Various distances, from zero, up to 44.3 *cm* from the detector surface are used in measurements, depending on the activity interval. The calibration of the system was also validated by the participation at international NPL-UK or IAEA exercises for the measurement of various volume samples, containing mixtures of radionuclides (Luca et al. 2010). The system is taken as reference for the dedicated HPGe spectrometer used in the radiopharmacy unit.

Role of the Radionuclide Metrology in Nuclear Medicine 157

of the laboratory. On the other hand, as a national provider of radioactive standards, the

(i) *Definition of Activities and Establishment of Traceability Chain.* Clear distinction of the two types of activities in relation with the RENAR accreditation was defined: Calibration activities and Testing activities. (a) The calibration branch required a sharp definition of the traceability chain and activities deployed in regime of quality management. The declared activities under accreditation are: (I) Attestation of the installations for the absolute (direct) standardization, mainly used for international comparisons, in order to prove the international equivalence of the Romanian standards, and for the preparation of standard sources and solutions used for the calibration of the secondary equipment. (II) Calibration and metrological check of the secondary installations for the relative (indirect) standardization. (III) Standardization of the radioactive standard sources and solutions. (IV) Preparation and relative or absolute standardization of radioactive sources and solutions, under the quality management system. The traceability chain continues outside the laboratory, in connection with the users, and implies: (V) The delivery of radioactive sources, with Calibration Certificates, under the quality management system. (VI) The calibration and metrological check of activity measurement installations. (VII) The organization of inter laboratory comparisons (ILCs) and proficiency tests (PTs) for the testing and calibration laboratories. (b) The testing branch of accredited activities refers at the Analysis of very low activity samples by the gamma-ray spectrometry. Another special aspect in the application of the requirements of the 17025:2005 Standard in our case is the responsibility of the National Nuclear Authority (CNCAN) regarding the radioprotection of the workers, public and patients. In this respect IFIN-HH, RML was CNCAN designed also

The calibration and metrological check of the equipment for measurement of the radioactivity imposed the development of technics for the preparation of a large variety of standard sources and solutions, to be used in-house, or delivered to the external customers which are performing radioactivity measurement. A general WP, coded AC-PL-LMR-10,

*Radioactive Solutions*. A large variety of radioactive solutions, physico-chemically stable, adequate as radioactivity standards, are prepared (Grigorescu et al.1975). Some of them, even for external users' delivery, are standardized absolutely, or alternatively, by the use of the calibrated ionization chamber. They are certified in terms of radioactive concentration, *Bq g*-1, and in total

*Point and Large Area Alpha and Beta Sources.* These sources are of immediate interest, both for calibration of contamination monitors (contaminometers), as well as for the effective measurement of the so called "Gross Alpha" and "Gross Beta" radioactive content of environmental, industrial and food chain samples. Their preparation and measurement of

The main requirements regarding the characteristics of the equipment for the measurement of activity and of the physico-chemical parameters were described in section 2. In order to satisfy them, a radionuclide metrology laboratory is asked to perform calibrations or other

describes the common operations and detailed WIs present the specific operations.

activity, *Bq,* per recipient, flame or mechanically sealed in glass ampoules or P6 vials.

the particle emission rate in a 2πsr geometry are described in (Sahagia et al. 1996a).

**5.2 Calibration and metrological check of measurement equipment** 

RML must meet quality requirements in their production.

as a notified calibration and testing laboratory for the nuclear field.

**5.1 Radioactive standards for nuclear medicine** 

Another use of the IFIN-HH, RML's spectrometric system is the precise determination of the emission intensity of gamma-rays for radionuclides of medical use. These parameters are of maximum importance for activity standardization by primary methods, as in most of measurements they are basic parameters in activity calculation. On the other hand, the efficiency and safety of the medical procedure depends directly on their precise knowledge. The precise value of half life is directly used in nuclear medicine units for the calculation of activity at the moment of administration. The calculation of patients' doses is based on the values of: activity, half life, radiations - types, energies and emission intensities. On the international scale, projects of the type*: "EURAMET.RI(II)-S5.Radionuclide"* are organized, for the experimental determination of emission intensities and evaluation projects coordinated by the Decay Data Evaluation Program (DDEP) are deployed. IFIN-HH, RML participates in both types of programs. For example, recently the laboratory participated at the exercise, organized for the new PET radionuclide 64Cu, EURAMET project 1085 (Bé et al. 2011). RML standardized absolutely solutions from 64Cu and 68Ga by the coincidence method (Sahagia et al. 2011). Point solid sources from standard solution were prepared gravimetrically, and were used for the determination of their decay parameters: gammarays emission intensities with the calibrated HPGe spectrometric system and half life by the use of the CENTRONIC IG12/20A ionization chamber (Luca et al.2011).
