Pharmaceutical requirements for RPhP

Nuclear imaging

Nuclear imaging is a section of medical radiology, which studies the methods of evaluation of a functional and morphological conditions of organs and systems by means of radiopharmaceutical products (RPhP).

As radioactive indicators, radionuclides with organic or nonorganic matter are used. Chemical compounds where the part of neutral atoms is replaced by radioactive are called, labeled compounds. Very small quantities of radionuclides (about 10^{-10 gram) are used. Such small quantities of radionuclides are named tracer (indicator) amount, and dozes of irradiation – tracer(indicator)} dozes. Such dozes don’t essentially disturb the functional condition of the patient and don’t break functions of vital processes. C ontra-indications are absent except for the restrictions stipulated by Ionizing Radiation Regulation-99: pregnancy, the period of lactation, childhood.

Chemical properties of radionuclides are identical to the properties of the same stable chemical elements; therefore their abilities in an organism are identical. Study of metabolism of radioactive indicators allows the study of metabolism of conforming stable chemical substances.

Radionuclides are produced in nuclear reactors, by means of cyclotrons. After clearing and defining specific activity the radionuclides are placed into hermetically sealed ampoules inside special protective containers and directed to radiological laboratories. The choice of the indicator and the equipment for nuclear evaluation depends on the purpose of evaluation.

Production of RPhP in the generator

Primary radionuclide of the generator: a protective casing, a column with primary radionuclide and system of communications (see fig. 9.1.). Secondary small-living radionuclide, which is formed as a result of radioactive decay of primary radionuclide, is washed away from the generator. The generator ^99mТс with a half-life period of 6 hours (primary radionuclide ⁹⁹Мо), ^87mSr with a half-life period 2,8 hours (primary radionuclide⁸⁷Y), ^113mIn with a half-life period of 99,8 minutes (primary radionuclide ¹¹³Sn, ¹³²I with a half-life period 2,3 hours primary radionuclide ¹³²Тe), etc is usually used.

Fig. 9.1. The scerch of nuclear generator.

Pharmaceutical requirements for RPhP

Chemical purity of RPhP is defined by a part of radionuclide which is present into RPhP in needed radioactive form.

Radiochemical purity is defined by a part of radionuclide, which is into the RPhP in the necessary chemical form. For example, if radiochemical purity of ¹³¹I – hippurane is 98 %, it means, that in a preparation there are 98 % of ¹³¹I, connected with hippuran. Radiochemical admixtures can influence the reliability (authenticity) of the resulted information.

Radionuclide purity -is a part of the general activity of the preparation, caused by necessary radionuclide.

Apyrogenic ability is provided with using of specific аpyrogenic reagents and solutions for preparation’s manufacture.

Sterility is provided with using of one among many methods of sterilization: it’s ultrafiltration, thermal sterilization, steam sterilization and other.

Radiotoxicity - a degree of damaging action of RPhP on an organism. According to the degree of radiation safety radionuclides are divided into 4 groups:

Group A – super radiotoxicity (in diagnostics it is not used);

Group B- high radiotoxicity (¹³¹I; ⁸⁹Sr);

Group C - average radiotoxicity (⁷⁵Se; ¹⁹⁸Au);

Group D- low radiotoxicity (⁵¹Cr; ⁶⁷Ga; ⁶⁴Cu).

Radionuclide is introduced in blood and first of all is distributed in the organism equally and then accumulating in some organs and tissues. All RPhP is divided into 3 groups: organotropic (^99mТс-pertechnat, ¹⁹⁸Au colloid, ¹⁹⁷Hg promeran), tumourotropnic (⁶⁷Ga citrate) and without the selective accumulation (²⁴Na). The criteria of nuclide’s radiotoxicity is the effective period of half excretion (T_exc).

For the registration of RPhP in an organism it is necessary that its radiation to be sufficient energy for registration by devices (50-150 KеV).

Таbl.9.1. Basic characteristics RPhP and radiation exposure on critical ograns.

Radionuclide	Т1/2	Compounds	Critical organ	Radiation dose, mSv/МBq
^32Р	14,3 days (-β)	The twice-substituted sodium phosphate	Organism as a whole Sexual glands Bone marrow	2,7 1,8 4,5
^67Ga	3,25 days	citrate	Bone marrow	0,15
^75Se	120,4 days	Selenium-methionine	Liver Kidneys	6,2 6,2
^99mTc	6 hours.	pertechnat, pyrophocphate, tetraphosmine, limfotsis	Liver Spleen Sexual glands Skeleton	0,092 0,057 0,0015 0,0094
^111In	2,8 days	citrin	Kidneys Bone marrow	0,016 0,0017
^113mIn	100 minutes	citrin	Liver Organism as a whole	0,10 0,0025
^131I	8,06 days	Potassium iodide	Thyroid gland Sexual glands Kidneys Organism as a whole Thick gut Liver	0,058 0,075 0,0049 9,4 0,22
^133Xe	5,29 days		Lungs Sexual glands	0,011 0,00035
^197Hg	64,1 hours.	promeran, labeled ^197Hg	Kidneys Sexual glands	3,1 0,011
^198Au	2,69 days	colloids	Liver Spleen Bone marrow	3,3 0,73

Ways of RPhP introduction into an organism: per os, intravenous, intra-arterial, in lymphatic vessels, intra-dermal, subcutaneous, interstitial, in the spinal channel, inhalation.

Requirements to RPhP for clinical use:

1. Radionuclide or its compounds, included in metabolism or are transferred by a current of blood, should display the functional condition of an organism or particular organ.

2. It should be harmless to an organism and quickly be excreted from it, that is Т eхс. – a time during which activity of the introduced RPhP will decrease twice due to disintegration and excretion from an organism (should be as short as possible). The best RPhP have Т eхс from 6-24 hours to10-30 days (radiation dose isn’t significant and time is enough to study the functional condition of an organism). It should not contain toxic admixtures or radionuclide, which during disintegration may form long-living radionuclides.

3. Radiopharmaceuticals should emit such particles or photons which are easy for registration with modern equipment. Alpha-nuclides are not suitable for diagnostic evaluations as a result of their short way in tissues. Gamma-emitting nuclides have received wide application: gamma-radiation is partially absorbed by tissues, gets outside and can be registered with radiometric devices.

The various products with ^99mТс are used widely in nuclear imaging for recognition of tumours, the study of central and peripheral haemodynamics, evaluations of a thyroid gland, bone system, etc. objects.

¹³¹I (Т 8 day), ¹³²I (Т 2, 2 hours) and their combinations are used for evaluation of function of the thyroid gland, liver and kidneys. ⁵¹Cr (Т 27 day) is used for evaluations in hematology. Colloid solutions and macrounits ^99mTc, ¹⁹⁸Au, ¹³¹I, ^113mIn (2, 6 day) are used for evaluation of the brain, liver, and lungs. ¹³³Xe is use for evaluation of function of lungs, peripheral haemodynamics, and a level of bloc age in sub-arachnidal spaces of the spinal cord. Compounds, labeled by ⁷⁵Se (Т 121 day), ³²P (Т 14, 3 day), ¹⁹⁷Hg (Т 65 hours), ^87mSr (Т 2, 8 hours), ¹⁹⁸Au (Т 2, 7 days), ⁶⁷Ga (Т 3, 2 days) are widely used in oncology (the basic sketch of radionuclide evaluation see fig 9.2).

Дата добавления: 2015-10-23