Medical Radiology and Radiation Safety. 2021. Vol. 66. № 5. P. 66–77

Topical Issues of Radiopharmaceuticals Appliance in PET Studies

A.V. Khmelev1,2 

1Research Institute – Federal research Center for Project Evaluation and Consulting Services, Moscow, Russia

2Russian Medical Academy of Continuous Professional Education, Moscow, Russiaa

Contact person: Aleksandr Vasilyevich Khmelev: This email address is being protected from spambots. You need JavaScript enabled to view it.



1. Requirements to radiopharmaceuticals

2. Factors affecting the biodistribution in organism

3. Uptake and localization mechanisms

4. Appliance in PET studies of biological processes and diagnostics

5. Aspects of regulation of radiopharmaceuticals circulation


Key words: radiopharmaceuticals, radionuclide, localization mechanism, PET 

For citation: Khmelev AV. Topical Issues of Radiopharmaceuticals Appliance in PET StudiesSupport of Occupational Radiation Protection during. Medical Radiology and Radiation Safety. 2021;66(5):66-77.

DOI: 10.12737/1024-6177-2021-66-5-66-77


1.Vallabhajosula S. Molecular Imaging: Radiopharmaceuticals for PET and SPECT. Berlin, Heidelberg: Springer-Verlag, 2009. 133 p.

2. Saha G.B. Basics of PET Imaging. Physics, Chemistry and Regulation. New York, Springer, 2010. 241 p.

3. Khmelev А.V. Positron Emission Tomography: Physical and Technical Aspects. Мoscow, Trovant Publ., 2016. 336 p. (In Russ.).

4. Zimmermann R.G. Industrial Constraints in the Selection of Radionuclides and the Development of New Radiopharmaceuticals. World J. Nucl. Med. 2008;7:126-34.

5. Qaim M. Development of Cyclotron Radionuclides for Medical Applications: from Fundamental Nuclear Data to Sophisticated Production Technology. In: WTTC15: Proceedings of WTTC15; 2014 Aug 18-21. Prague, Czech Republic Publ., 2014. P. 18-20.

6. Khmelev А.V. Analysis of Positron Emission Tomography Providing with Radionuclides. Medical Radiology and Radiation Safety. 2019;64;6:70-81. (In Russ).

7. Kodina G.E., Krasikova R.N. Methods of Production of Radiopharmaceuticals and Radionuclide Generators for Nuclear Medicine. Мoscow, Izdat. Dom MEI Publ., 2014. 282 p. (In Russ.).

8. Davidson C.D., Phenix C.P., Tai T.C., Khaper N., Lees S.J. Searching for Novel PET Radiotracers: Imaging Cardiac Perfusion, Metabolism and Inflammation. Am. J. Nucl. Med. Mol. Imaging. 2018;8;3:200-27. PMID: 30042871. PMCID: PMC6056242.

9. Wadsak W., Mitterhauser M. Basic and Principles of Pharmaceuticals for PET/CT. E.J.R. 2010;73:461-469. DOI: 10.1016/j.ejrad.2009.12.022. PMID: 20181453.

10. Miller P.W., Long N.J., Vilar R., Gee A.D. Synthesis of 11C, 18F, 15O and 13N Radiolabels for Positron Emission Tomography. Angew. Chem. Int. Ed. 2008;47:8998-9033. DOI: 10.1002/anie.200800222. PMID: 18988199.

11. Zimmermann R.G. Why Are Investors not Interested in My Radiotracer? The Industrial and Regulatory Constraints in the Development of Radiopharmaceuticals. Nucl. Med. Biol. 2013;40:155-166. DOI: 10.1016/j.nucmedbio.2012.10.012. PMID: 23218796.

12. Lau J., Rousseau E., Kwon D., Lin K.-S., Bénard F., Chen X. Insight Into the Development of PET Radiopharmaceuticals for Oncology. Cancers. 2020;12;5:1312-1365. DOI: 10.3390/cancers12051312. PMID: 32455729. PMCID: PMC7281377.

13. Mourtada F., Sims-Mourtada J., Azhdarinia A., Yang D.J. Regulatory Requirements for PET Radiopharmaceuticals Production: Is Automation an Answer? Current Medical Imaging. 2008;4;1:28-33. DOI: 10.2174/157340508783502804.

14. Vallabhajosula S., Killeen R.P. Osborne J.R. Altered Biodistribution of Radiopharmaceuticals: Role of Radiochemical/Pharmaceutical Purity, Physiological, and Pharmacologic Factors. Semin. Nucl. Med. 2010;40:220-241. DOI: 10.1053/j.semnuclmed.2010.02.004  PMID: 20513446.

15. Ziessman H., O'Malley J. Nuclear Medicine: the Requisites. Philadelphia, Saunders, 2014. 464 p.

16. Kamkaew A., Ehlerding E.B., Cai W. Nanoparticles as Radiopharmaceutical Vectors. Radiopharmaceutical Chemistry. Eds. Lewis J., Windhorst A., Zeglis B. New York, Springer, Cham, 2019. P. 181-203.

17. Lee Y.S. Radiopharmaceuticals for Molecular Imaging. The Open Nuclear Medicine Journal. 2010;2:178-185. 

18. Jeong J.M. Application of a Small Molecule Radiopharmaceutical Concept to Improve Kinetics. Nucl. Med. Mol. Imaging. 2016;50:99-101. DOI: 

19. Waterhouse R.N. Determination of Lipophilicity and Its Use as a Predictor of Blood-Brain Barrier Penetration of Molecular Imaging Agents. Mol. Imaging. Biol. 2003;5;6: 376-89. DOI: 10.1016/j.mibio. 2003.09.014  PMID: 14667492.

20. Silindir M., Özer A.Y. Recently Developed Radiopharmaceuticals for Positron Emission Tomography (PET). Fabad. J. Pharm. Sci. 2008;33:153-62.

21. Colom M., Vidal B., Zimmer L. Is there a Role for GPCR Agonist Radiotracers in PET Neuroimaging? Front. Mol. Neurosci. 2019;12:255-94. DOI: 10.3389/fnmol.2019.00255. PMID: 31680859. PMCID: PMC6813225. 

22. Komal S., Nadeem S., Faheem Z., Raza A., Sarwer K., Umer H., et al. Localization Mechanisms of Radiopharmaceuticals. 2020. Available from: DOI:10.5772/intechopen.94099.

23. Ponto J.A. Mechanisms of Radiopharmaceutical Localization. Ed. Norenberg J. UNM Сollege of pharmacy. 2012;16;4:2-35.

24. Lim M.M.D., Gnerre J., Gerard P. Mechanisms of Uptake of Common Radiopharmaceuticals. RadioGraphics Fundamentals |Online Presentation. Radiographics. 2018;38;5:1550-51. Available from:

25. Kilian K. 68Ga-DOTA and Analogs: Current Status and Future Perspectives. Rep. Pract. Oncol. Radiother. 2014;19:13-21. DOI: 10.1016/j.rpor.2014.04.016. PMID: 28443194.

26. Huang Y.Y. An Overview of PET Radiopharmaceuticals in Clinical Use: Regulatory, Quality and Pharmacopeia Monographs of the United States and Europe. 2018. Available from: https:// /books/nuclear-medicine-physics/an-overview-of-pet-radio pharmaceuticals-in-clinical-use-regulatory-quality-and-pharmacopeia-monograp. DOI:10.5772/intechopen.79227. 

27. Perk L.R., Stigter-van Walsum M., Visser G.W., Kloet R.W., Vosjan M.J.W.D., Leemans C.R., et al. Quantitative PET Imaging of Met-Expressing Human Cancer Xenografts with 89Zr-Labelled Monoclonal Antibody DN30. Eur. J. Nucl. Med. Mol. Imaging. 2008;35:1857-1867. Available from:

28. Brooks A.F., Drake L.R., Stewart M.N., Cary B.P., Jackson I.M., Mallette D.,  et al. Fluorine-18 Patents (2009–2015). Part 1. Novel Radiotracers. Pharm. Pat. Anal. 2016;5;1:17-47. DOI: 10.4155/ppa.15.36. PMID: 26670619. PMCID: PMC5561792.

29. Pagani M., Stone-Elander S., Larsson S.A. Alternative Positron Emission Tomography with Non-Conventional Positron Emitters: Effects of Their Physical Properties on Image Quality and Potential Clinical Applications. Eur. J. Nucl. Med. 1997;24;10:1301-1327. DOI: 10.1007/s00259 0050156. PMID: 9323273.

30. Jødal L., Le Loirec С., Champion С. Positron Range in PET Imaging: Non-Conventional Isotopes. Physics in Medicine and Biology. IOP Publishing. 2014;59:7419-34. Available from:

31. Jung J., Ahn B.-C. Current Radiopharmaceuticals for Positron Emission Tomography of Brain Tumors. Brain Tumor Res Treat. 2018;6;2:47-53. DOI: 10.14791/btrt.2018.6.e13.PMID: 30381916. PMCID: PMC62 12689.

32. Zykov E.M., Pozdnyakov A.V., Kostenikov N.A. Efficient Use of PET and PET/CT in Oncology. Practical Oncology. 2014;15;1:31-6 (In Russ.).

33. Lopci E., Grassi I., Chiti A., Nanni C., Cicoria G., Toschi L., et al. PET Radiopharmaceuticals for Imaging of Tumor Hypoxia: a Review of the Evidence. Am. J. Nucl. Med. Mol. Imaging. 2014;4;4:365-384. PMID: 24982822. MCID: PMC4074502.

34. Andersson J.D., Halldin C. PET Radioligands Targeting the Brain GABAA/Benzodiazepine Receptor Complex. J. Label. Compd. Radiopharm. 2013;56:196-206. DOI: 10.1002/jlcr.3008. PMID: 24285326.

35. Meisenheimer M., Saenko Yu., Eppard E. Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging- a Lot to Consider. 2019. Available from: isotopes/gallium-68-radiolabeling-of-radiopharmaceuticals-for-pet-imaging-a-lot-to-consider. IntechOpen. DOI: 10.5772/intechopen.90615.

36. Weineisen M., Schottelius M., Simecek J., Baum R.P., Yildiz .A., Beykan S., et al. 68Ga- and 177Lu-labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. J. Nucl. Med. 2015;56;8:1169-1176. PMID: 26089548. DOI: 10.2967/jnumed.115.158550.

37. Werner R.A., Bluemel C., Allen-Auerbach M.S., Higuchi T., Hermann R. 68Gallium- and 90Yttrium-/ 177Lutetium: “Theranostic Twins” for Diagnosis and Treatment of NETs. Ann. Nucl. Med. 2015;29:1-7. DOI:

38. van de Watering F.C.J., Rijpkema M., Perk L., Brinkmann U., Oyen W.J.G., Boerman O.C., et al. Zirconium-89 Labeled Antibodies: a New Tool for Molecular Imaging in Cancer Patients. Biomed. Res. Int. 2014;2014;203601. DOI: 10.1155/2014/203601. PMID: 24991539.

39. Dijkers E.C., Kosterink J.G., Rademaker A.P., Perk L.R., van Dongen G.A.M.S., Bart J., et al. Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/New ImmunoPET Imaging. J. Nucl. Med. 2009 50:974-981. PMID: 19443585 DOI: 10.2967/jnumed.108. 060392. 

40. Mahajan S., Divgi C.R. The Role of Iodine-124 Positron Emission Tomography In Molecular Imaging. Clin Transl Imaging. 2016;4;4:297-306. PMID: 27158012. DOI: 10.1016/j.cpet.2008.05.001.

41. FDA-Approved Radiopharmaceutical. Cardinal Health. 2019. Rev. 21/6.26.20. Available from: dam/corp/web/documents/fact-sheet/cardinal-health-fda-approved-radiopharmaceuticals.pdf.

42. Clarke B.N. PET Radiopharmaceuticals: what’s New, what’s Reimbursed, what’s Next? J. Nucl. Med. Tech. 2018;46;1:12-16. PMID: 29438008. DOI: 10.2967/jnmt.117.205021. 

43. Zelinskaya E. Radiopharmacy – Unique Trending of Pharmaceutic Industry. GMP News. 2018;2;16:55-70 (In Russian).

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Conflict of interest. The author declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors

Article received: 23.12.2020. 

Accepted for publication: 20.01.2021.