Current Trends in Radio- Pharmaceuticals

 

Rana Khan^1*, Aizaz Ahmed Khan², Nuha Rasheed³, Abdul Saleem Mohammad⁴

¹Department of Pharma. D, Nizam Institute of Pharmacy, Deshmukhi (V), Pochampally (M), Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

²Department of Engineering and Technology, Nizam Institute of Engineering and Technology, Deshmukhi (V), Pochampally (M), Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

³Department of Pharmaceutics, Nizam Institute of Pharmacy, Deshmukhi (V), Pochampally (M), Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

⁴Department of Pharmaceutical Analysis and Quality Assurance, Nizam Institute of Pharmacy, Deshmukhi (V), Pochampally (M), Behind Mount Opera, Yadadri (Dist)-508284, Telangana, India.

 

ABSTRACT:

The development of radiotraces with defined affinities for specific receptor systems is a potentially useful approach to the design of radio pharmaceuticals for nuclear medicine. Radio labeled ligands, such as hormones and neurotransmitters, are being synthesized and evaluated as diagnostic tools for diseases which can be characterized either by changes in receptor concentration or by novel receptor expression. Since the utility of a radio pharmaceutical is dependent upon the achievement of adequate ratios of target to non-target accumulation of radio activity, design of radio traces via the receptor approach attempts to exploit those systems in which receptor is present in significantly higher concentration at potential target sites such as tumors. Receptor-mediated radio tracers are also currently being used in animal models to investigate the normal tissue distribution of drug and hormone receptors and the in-vivo pharmacokinetics of receptor binding. The successful development of receptor-avid radiopharmaceuticals will depend upon the ability to synthesize ligands of high specific radio activity which retain the high affinity and binding specifically for the receptor after radio labeling.

 

 

 

INTRODUCTION:

Radioactive substances having a common property of emitting rays or particles which effect photographic plates even when they are protected from visible direct light and also bring about discharge of electrified bodies.

About 40 radioactive elements are known which are arranged into families such as uranium series, thorium series and actinium series. The elements are turned as radioactive because they are unstable and undergo spontaneous decomposition accompanied by emmition of radiations or rays. The emmition of radiations by radioactive substances is not influenced by temperature, pressure, concentration and catalyst ^[1-3]. Numerous advances in radio pharmaceuticals synthesis, quality assurance and regulatory control have occurred in recent years and are continuing to develop. Advances have been clearly observed for those pharmaceutics based on positron and radio halogen radioisotope. This includes radio pharmaceutics for the heart, brain and adrenal glands. Exciting results are obtained with radio labellled compounds of high specific activity that bind to tissue receptors. The feasibility of imaging receptor in the brain has been, also, demonstrated. Technenium-99 agents have progressed from the applications of crude, largely un-characterized chemistry to probe the functional level of organs such as lungs, liver and kidneys to the development of radio pharmaceutics based on a solid structural chemistry foundation. Other branching fields such as use of liquid chromatography automation and computer applications have gained a trevendous momentum and exhibited a big leap to enter the 90”s with an increasing number of applications^[4-6]. When we look at a vast majority of research and development in the field of radio pharmaceutics, we can pin point major trends such as:

·        Development, testing and evaluation of new tracers emphasizing receptor targeting.

·        Quality assurance as an integral feature of radiopharmaceutical production.

·        Setting software and hardware for production and quality control and compartmental modeling.

·        Establishing protocols at regulatory measures to ensure save and efficient production and delivery of radio pharmaceutics.

·        Investigation and evaluation of the economy aspects of production and application of radio pharmaceutics ^[5-7].

 

The above areas, in general are tackled in the major part by nuclear chemists, radio chemists and radiopharmaceutical chemists with a wide diversity of specialized training and experience in biochemistry, pharmacology, and toxicology, computer sides and engineering. This reflects the leading role of well established chemists in this great progress. The continuation such vital task, however, is the responsibility of new generation of chemists whom we solicite their contribution this field by developing their professional interest into dedicated carriers. The purpose of this work, therefore, is to review the status of the new trends in the development, testing, application and regulation of radio pharmaceutics for all of us to be aware of what is new and for the new generation of chemists to be acquainted with such review to investigate new areas for carrier development in radiopharmaceutical sciences ^[7-9].

 

●Radiopharmaceutical In Therapeutics:

Radiopharmaceutical are used as therapeutic agents (frequently known as RPTs) are designed to deliver high doses of radiation to selected malignant sites in target organs or tissues, while minimizing the radiation doses to surrounding healthy cells. Over the past several years, several types of RPTs with special properties, including compounds for labeling monoclonal antibodies, have been used in animal and human clinical trials with promising results. Many radio labeled particles, microspheres and liposomes are appropriate for therapy, once the encapsulated diagnostic radioisotope has been exchanged for therapeutic one from the α- or β- emitter group. The modern trend in radiopharmaceutical research for oncology is development of RPTs that may be said to be tumour – seeking and tumour specific. In therapeutic radiopharmaceuticals application – unlike the case of external radiation therapy where the radiation from an external sealed radioactive sources is focused on the site to be irradiated- the product is administered to patient orally or intravenously and is selectively taken up or localized in the site to be irradiated. External beam radiation requires about ten treatments over a period of 30 days to deliver a dose of 2000 to 2500 radicals (rads). In contrast, therapeutic radiopharmaceuticals safely deliver an average dose of 15000 rads in single treatment with minimal damage to healthy surrounding tissues. Currently this novel approach is finding success in fighting different cancers viz. liver, head and neck cancer, spleen cancer etc.

 

●Alpha Rays:

Among alpha-particles emitters, only two radio nuclides have been considered and studied as potential therapeutic agents: astatine-211 and bismuth-212. Largely because of the extremely high radio toxicity and short half-lives of alpha emitting RPTs, a good deal of laboratory research still is needed to develop them for medical therapy uses.

 

●Beta Rays:

Radio nuclides that emit beta particles are the only ones that have been used in therapeutic nuclear medicine. This is due to various reasons. Beta particles have penetration ranges in the tissue on the order of millimeters to a few centimeters, appropriate depths for the irradiation of small to medium sized tumours. Secondly, some of the most promising beta- emitting radio nuclides have desirable half-lives, varying from several hours to days. Lastly, many of these radio nuclides are easily. Produced in nuclear research reactors, facilitating their availability. Radio nuclides emitting beta particles are widely used. They include phosphorus-32, strontium-89, and iodine- 131, which might be considered the “first generation” of therapeutic radio nuclides. Among the “second generation” of beta emitting RPTs are samarium-153, rhenium-186, copper-67, and holmium-166.

 

●Gamma Rays:

Gamma radiation exhibits low values of linear energy transfer, as it penetrates relatively deeply, on the order of several centimeters, and does not deposit much energy along its track. Consequently, pure gamma-emitting radionuclides usually are not used for therapeutic purposes ^[6-9].

 

SUMMARY/CONCLUSION:

The development of radio traces with defined affinities for specific receptor systems is a potentially useful approach to the design of radio pharmaceuticals for nuclear medicine. Radioactive substances having a common property of emitting rays or particles which effect photographic plates even when they are protected from visible direct light and also bring about discharge of electrified bodies.

 

Radiopharmaceutical are used as therapeutic agents (frequently known as RPTs) are designed to deliver high doses of radiation to selected malignant sites in target organs or tissues, while minimizing the radiation doses to surrounding healthy cells. Period of 30 days to deliver a dose of 2000 to 2500 rads.

 

In contrast, therapeutic radiopharmaceuticals safely deliver an average dose of 15000 rads in single treatment with minimal damage to healthy surrounding tissues. Therapeutic radiopharmaceutical are very stable and have a proven efficacy in the field of treatment of diseases especially cancer. These therapeutic radiopharmaceuticals serve as one of the future materials in the battle against cancer and tumors.

 

Numerous advances in radio pharmaceuticals synthesis, quality assurance and regulatory control have occurred in recent years and are continuing to develop. Advances have been clearly observed for those pharmaceutics    based on positron and radiohalogen radioisotope. This includes radio pharmaceutics for the heart, brain and adrenal glands. Exciting results are obtained with radio lapelled compounds of high specific activity that bind to tissue receptors. The feasibility of imaging receptor in the brain has been, also, demonstrated.

 

The purpose of this work, therefore, is to review the status of the new trends in the development, testing, application and regulation of radio pharmaceutics for all of us to be aware of what is new and for the new generation of chemists to be acquainted with such review to investigate new areas for carrier development in radiopharmaceutical sciences.

 

REFERENCES:

1.       Pharmaceutical Chemistry Inorganic: Vol 1 by G.R. Chatwal

2.       Pharmaceutical Chemistry: Theory and Practical by Vn Rajasekaran

3.       Inorganic Chemistry, Robert M. Kren, Harold W. Dodgen, Carl J. Nyman, Herbert Bradford Thompson, Lawrence S. Bartell, John K. Wittle, Grant Urry.

4.       “Qualitative Chemical Analysis – Organic and Inorganic” by F. Mollwo Perkin

5.       "Inorganic Chemistry" by William Allen Miller

6.       The Medicines Act 1968 (Application to Radiopharmaceutical-associated Products) Regulations.London:HMSO;1992.www.legislation.gov.uk/uksi/1992/605/contents/made (accessed 3 June 2011).

7.       Theobald T. Sampson’s Textbook of Radio pharmacy. 4th edition. London: Pharmaceutical Press; 2011.

8.       Administration of Radioactive Substances Advisory Committee. Notes for guidance on the clinical administration of radiopharmaceuticals and use of sealed radioactive sources. March 2006. www.arsac.org.uk/notes_for_guidance (accessed 3 June 2011).

9.       International Commission on Radiological Protection. Radiation dose to the patient from radiopharmaceuticals. Annals of the ICRP 1988; 18: issues 1–4.

 

 

 

Received on 08.12.2016       Accepted on 15.01.2017     

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