**7. Generators**

In Nuclear Medicine environment, sometimes is useful to have a regular provision of radioisotopes for studies to be performed without the restrictions of providers time dependences, for example when studies has to be done anytime of the day in emergency conditions. If physician suspects an infection in a patient admitted in Emergency Room, it will be of utmost usefulness to have Nuclear Medicine images done with appropriate radiopharmaceuticals to solve the question about the most effective treatment to be offer to the patient. Either way, sometimes in Cardiology it is of high importance to know about percentage of isquemic muscle, but patient has not the luxury of time to undergo a catheterism, so it is more effective and quick to have Nuclear Medicine images and cine of the heart. In many cases like this, have a good availability of radiotracers make the differences between a correct and opportune answer or a misdiagnosis.

This is the reason why radioisotopes generators have become so popular beside the fact that in countries like Venezuela where there is no nuclear production, sometime become very hard to warranty a regular supply. A radioisotopes generator is a device in which you can contain a pair father/daughter in which the daughter is the product of interest for studies purposes and father only come to generate the full amount of daughter needed. Due to the short half life we need for the radioisotope to be safe handle in hospital conditions, it would be useful to find a pair father and daughter that warranty the in time provision of radioisotope needed. During the generator useful life father has to decay completely to the useful daughter so it can be easily recharged, disposed or returned to provider. Such pair must that accomplish some conditions like:


reactors is that in cyclotron you can use 98Mo enriched target to be activated by neutron irradiation in a (n,γ) reaction, while 99Mo coming from fission include very expensive production beside the complex regulations due to the highly enriched Uranium targets.

(CaNa399mTc)

Calcium Gluconate Lactobionate

Calcium Glucoheptonate

2,4 dimercaptosuccinic acid

Sodium Calcium Phytate

Albumin Macroagregates Microspheres (50μ)

(MDP) Metilendiphosphonate

HIDA (Hepatobiliary IminoDiacetic Acid)

99mTc HMPAO (HexaMethylPropileneAmineOxime)

Monofluorphosphate Diphosphonate Pirophospate

Microspheres (0.5-4 μ)

Tetracycline Citrate

**TARGET ORGAN 99mTc RADIOPHARMACEUTICALS Brain** DTPA (DiethylTriaminoPentacetic Acid)

**Kidneys** DTPA (DiethylTriaminoPentacetic Acid)

Manitol Dextrose Penicilamine

Sn Hidroxide Sodium Phytate

**Brain Perfusion** ECD (EthylCysteinate Dimer)

**Liver** 99mTc Sulphur

**Bone** Poliphosphate

**Dynamic Studies** Albumina

**Tumors** Bleomicine

**Spleen** Red Blood Cell Markers **Spleen and Bile** Vitamine B6 glutamic

Table 4. Radiuopharmaceuticals used with 99mTc for diagnostic studies.

**Blood Pool** 99mTc Albumina

**White Blood Cell or platelets (infection or inflammation)** 

**Lungs** Inorganic Macroagregate


After radiochemist discover some pairs of father/daughter that accomplish this characteristics, some were built in a shielded container to be send to hospital to extract the daughter. It makes radiosotopes clinically useful and commercially available.

Medicine is not the only client for radioisotopes generator, also we will talk about some other uses of them that are increasing its popularity thru years. So let´s have a few words about their relationship. As in any father/daughter relationship there are different kinds, in radioactive "family" we can talk about two kind of equilibrium that this families reach, they are called transient and secular equilibrium. Equilibrium meaning when father and daughter exist in significant proportion to one another. Secular equilibrium is a condition that they can reach when father physical half life is 2 or 3 magnitude orders greater that daughter´s (100 to 1000 times greater). It means when daughter decay many times father seems no to be affected. While transient equilibrium is a condition that is reach when father physical half life is about 10 times daughter´s. It is, when daughter decay few times father can decay to its 50%, i.e a full half life. Note that if physical half life of the daughter is larger that the father equilibrium can never be reach because father will be ever alone.

#### **Secular Equilibrium Generators**

$$\begin{aligned} ^{68}G & \xrightarrow{\varepsilon, 275d} ^{68}Ga \xrightarrow{\beta^{+}, \varepsilon, \gamma, 1.14} ^{h} ^{68}Zr \\\\ ^{81}Rb & \xrightarrow{\beta^{+}, \varepsilon, 4.7h} ^{61m}Kr \xrightarrow{\gamma, 13s} ^{61}Kr \\\\ ^{82}Sr & \xrightarrow{\varepsilon, 25d} ^{62}Rb \xrightarrow{\beta^{+}, \varepsilon, \gamma, 75s} ^{62}Kr \\\\ ^{113}Sn & \xrightarrow{\varepsilon, 118d} ^{113m}In \xrightarrow{\gamma, 1.7h} ^{113}In \end{aligned}$$

#### **Transient Equilibrium Generators**

$$^{99}Mo \xrightarrow{\beta^{-} \cdot \chi, 67h} ^{99m}Tc \xrightarrow{\chi, 6 \cdot h} ^{99}Tc$$

$$^{198}W \xrightarrow{\varepsilon, 275d} ^{198}Rh \xrightarrow{\beta^{-}, 17 \cdot h} ^{198}Os$$

Although this last one has a promising future in metastatic disease pain reliever and as a monoclonal antibody marker, the most popular generator in Nuclear Medicine is the Mo/Tc one. It is Techenetium is highly biocompatible in the Nuclear Medicine fashion so it can be used in a large number of studies.

This Mo/Tc generators can be produced in cyclotrons or reactors and as in many radioisotope produced, the advantages of using that from cyclotron in front of that of

5. This separation must be passive in terms of no violent chemical reaction must be

6. The daughter must be eluted with a human compatible solution to warranty biological

7. The human intervention would be minimum to warranty the minimum exposure to

8. Radiation protection now is not the unique concern but chemical and biological

After radiochemist discover some pairs of father/daughter that accomplish this characteristics, some were built in a shielded container to be send to hospital to extract the

Medicine is not the only client for radioisotopes generator, also we will talk about some other uses of them that are increasing its popularity thru years. So let´s have a few words about their relationship. As in any father/daughter relationship there are different kinds, in radioactive "family" we can talk about two kind of equilibrium that this families reach, they are called transient and secular equilibrium. Equilibrium meaning when father and daughter exist in significant proportion to one another. Secular equilibrium is a condition that they can reach when father physical half life is 2 or 3 magnitude orders greater that daughter´s (100 to 1000 times greater). It means when daughter decay many times father seems no to be affected. While transient equilibrium is a condition that is reach when father physical half life is about 10 times daughter´s. It is, when daughter decay few times father can decay to its 50%, i.e a full half life. Note that if physical half life of the daughter is larger

involved in the process, to warranty the chemical safeness

9. The granddaughter must be of very long time as to be consider stable

daughter. It makes radiosotopes clinically useful and commercially available.

that the father equilibrium can never be reach because father will be ever alone.

ሱۛۛۛሮ ܩܽ <sup>ఉ</sup>శǡఌǡఊǡଵǤଵସ ሱۛۛۛۛۛۛۛۛሮ ܼ݊ ଼ ଼ ଼

ሱۛۛۛۛۛሮ ݎܭ ఊǡଵଷ௦ ሱۛۛሮ ݎܭ ଼ଵ ଼ଵ ଼ଵ

ሱۛۛሮ ܴܾ <sup>ఉ</sup>శǡఌǡఊǡହ௦ ሱۛۛۛۛۛۛሮ ݎܭ ଼ଶ ଼ଶ ଼ଶ

ሱۛۛۛሮ ܫ݊ ఊǡଵǤ ሱۛۛۛሮ ܫ݊ ଵଵଷ ଵଵଷ ଵଵଷ

ሱۛۛۛۛۛሮ ܶܿ ఊǡ ሱۛሮ ܶܿ ଽଽ ଽଽ ଽଽ

ሱۛۛۛሮ ܴ݄ <sup>ఉ</sup>షǡଵ ሱۛۛۛۛሮ ଵ଼଼ ଵ଼଼ ܱݏ ଵ଼଼ Although this last one has a promising future in metastatic disease pain reliever and as a monoclonal antibody marker, the most popular generator in Nuclear Medicine is the Mo/Tc one. It is Techenetium is highly biocompatible in the Nuclear Medicine fashion so it can be

This Mo/Tc generators can be produced in cyclotrons or reactors and as in many radioisotope produced, the advantages of using that from cyclotron in front of that of

ܩ݁ ఌǡଶହௗ

ܴܾ <sup>ఉ</sup>శǡఌǡସǤ

ఌǡଶହௗݎܵ

ܵ݊ ఌǡଵଵ଼ௗ

ܯ

ܹ ఌǡଶହௗ

ఉషǡఊǡ

safeness

radiation

protection is also very critical

**Secular Equilibrium Generators** 

**Transient Equilibrium Generators** 

used in a large number of studies.

reactors is that in cyclotron you can use 98Mo enriched target to be activated by neutron irradiation in a (n,γ) reaction, while 99Mo coming from fission include very expensive production beside the complex regulations due to the highly enriched Uranium targets.


Table 4. Radiuopharmaceuticals used with 99mTc for diagnostic studies.

• Stability

• Target effectiveness • Activation effectiveness

• Area monitorization • Personal dosimetry • Activation control • Airborne debris • Chimney

• Shielding

**accounting to:** 

• Output dose and exposition

• Area classification and signs

• Personnel Medical Check up:

• Radiation Safety Committee

• Radioisotope Production

• Possible emergency

• Pre-start conditions

• Decay rate • Free release dates

• Fractionation doses

• Beam Energy • Output flux

• Mechanical movements of inner and outer doors

**8.1.3 Radiation Safety aspects to be under control are:** 

• Previous to begin working in the facility

• Posterior to end laboral relationship with the facility

**8.1.4.1 In radioisotope production it must be carefully checked:** 

• Area and ventilation ducts monitoring during cyclotron is on • Activation and contamination control after cyclotron is turn off

• Radioactive waste disposal entry and release record

**8.1.4.2 Radioactive material handling for diagnostic studies** 

**8.1.4 Daily journey: Also three aspects need to be controlled step by step,** 

• Annual (prevocational) check up

• Handling radioactive material for studies

• Fractionation residues and contamination

• Total activity produced in a cyclotron run

• Patient injection site and procedure

• Pre and post Hot Cell monitoring

• Radioactive waste disposal • Place design • Waste classification
