Nuclear Medicine Procedures in Clinical Research: Safety, Standards, and Regulatory Oversight

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Nuclear Medicine Procedures in Clinical Research: Safety, Standards, and Regulatory Oversight - Axcellant

Nuclear Medicine Procedures in Clinical Research: Safety, Standards, and Regulatory Oversight

  1. sie 04, 2025

What Are Nuclear Medicine Procedures and How Are They Used in Clinical Trials?

Nuclear medicine procedures (NMPs) are diagnostic and/or therapeutic techniques using drugs labelled with radionuclides (e.g., 18F, 99mTc, 131I), such as PET and SPECT imaging techniques, radioactive iodine testing/therapy, and many others. As many NMPs carry both therapeutic and diagnostic potentials, nuclear medicine is strongly associated with the so-called theranostic approach. It has been observed significant increase of interest in theranostics as a part of personalized medicine.

In basic and clinical trials, nuclear medicine procedures may be the main subject of research or serve as a tool to measure the efficacy of other treatments. Therefore, NMPs are useful in various medical areas, from medical imaging to oncology, hematology, cardiology, neurology, gastroenterology etc.

Regulatory and Ethical Frameworks Governing the Use of Radiopharmaceuticals (FDA, EMA, IAEA)

The majority of our clients lead their pre-clinical and clinical trials within the EU or America, where they must adhere to strict laws and ethical standards[i],[ii]. The European and the US regulations are set out in federal and member state laws. Practical requirements are covered in detailed guidelines developed by the main medicine-related regulatory bodies – the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

Europe: EMA and EANM

The European regulations on nuclear medicine procedures must follow the Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use and the Council Directive 2013/59/EURATOM of 5 December 2013, laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation. The examples of practical guidelines, blueprints, and requirements, drafted by EMA and other organizations, are listed below:

  • The EMA scientific guidelines on non-clinical and clinical requirements for radiopharmaceuticals[iii],[iv],
  • A series of EMA general guides on testing and registering new drugs or medical devices, as well as the post-authorization management thereof[v],
  • European Nuclear Medicine Guide (2018 and 2020) – a comprehensive manual on therapeutic and diagnostic uses of radiopharmaceuticals published by the European Association of Nuclear Medicine, a non-profit NGO since 1985[vi].

The USA: FDA and NRC

The US FDA operates under the 21 CRF and defines standards for medical imaging and drug development, along with practical guidance for industry[vii]. Like other drugs, new radiopharmaceuticals are subject to the regular authorization pathway, including pre-clinical trials, submitting the Investigational New Drug (IND) application, clinical trials, and New Drug Application (NDA), as well as review and approval by the FDA[viii].

The FDA also has a special Radioactive Drug Research Committee (RDRC) program that “under 21 CFR 36 1.1 permits basic research using radioactive drugs in humans without an IND when the drug is administered under [the specified] conditions”[ix].

Note: Any use of radioactive materials in the USA must also be approved and supervised by the Nuclear Regulatory Commission (NRC)[x].

Worldwide: IAEA

To unify the radiation protection guidelines globally and facilitate intergovernmental collaboration, the International Atomic Energy Agency (IAEA) provides rules and guidelines for entities involved in nuclear medicine procedures, e.g., the manual “Good Practice for Introducing Radiopharmaceuticals for Clinical Use”[xi].

Navigating the legislation labyrinths across various jurisdictions may be confusing and time-consuming. Contact us to find out which regulations are relevant to your research project.

Common Nuclear Medicine Procedures in Research: SPECT, PET, and Hybrid Imaging     

The most widely utilized NMPs are Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET). The techniques differ in terms of resolution, required radionuclides and equipment, cost, and applicability. However, both rely on measuring gamma radiation emitted from the radiopharmaceuticals (radiotracers) introduced to the patient’s body. Depending on the type, radiotracers are accumulated in different parts of the body where they can be detected. Compared to regular medical imaging methods (like CT, MRI, US, or X-ray), NMPs show how specific organs function rather than what they look like. However, modern devices let us combine SPECT or PET with other imaging techniques into so-called hybrid imaging methods. It results in, e.g., PET/CT or SPECT/MRI, or other combinations. Hybrid techniques provide more information during a single procedure, saving time and resources, and limiting the radiation exposure.

Radiation Safety, Dosimetry, and Patient Risk Management

All nuclear medicine procedures involve radiation exposure for patients, medical personnel, and the environment. Also, every case must be assessed to determine if the benefits for the patient outweigh the overall risk. Therefore, consistent and careful dosimetry protocols must be developed and applied for every person involved to ensure that the accepted radiation limits are not exceeded.

Practical safety and risk-management rules have been developed to help with the trials and care design, for example:

  • Detailed IAEA Safety Standards[xii],
  • Comprehensive IAEA resources on the Radiation Protection of Patients (RPOP)[xiii],
  • EANM guideline on quality risk management for radiopharmaceuticals[xiv].

Operational Considerations for CROs: Logistics, Documentation, and Qualified Facilities 

NMPs require a reliable supply of radionuclides, technically advanced facilities, qualified personnel, as well as safety measures in place. It is particularly relevant for clinical trials, where the unknown facets are more pronounced than in standard care. Therefore, organizing nuclear medicine research is very demanding. For every trial, all steps must be carefully planned, organized, and documented:

  • efficient collaboration, communication across engaged cross-functional departments
  • management and flow of the study product
  • relevant certifications from local governments for radionuclide
  • necessary equipment and assessment to meet study needs
  • the source, transportation, and storage of radionuclides,
  • careful analysis of patient’s path in different clinics e.g. oncology and nuclear medicine.

A breach or neglect in any area may pose a challenge to keep study timelines and achieve any expected milestones. Contact us to learn how to coordinate all the logistical, formal, and practical aspects of your trial.

The Evolving Role of Nuclear Medicine in Drug Development and Personalized Therapies

Despite the apparent challenges, multiple research centers include NMPs in their protocols. Why does it pay off? First, nuclear medical imaging provides incomparable insight into the structure, functioning, and response of tissues/organs to the tested treatments. Second, many substances can be radiolabeled and used as tracers or drug delivery systems, including antibodies and targeted biological drugs, anticancer chemotherapy, and/or radiotherapy agents etc. And finally, radiopharmaceuticals, with their diagnostic and therapeutic potential, make the theranostic approach an increasingly expanding area of nuclear and personalized medicine.

Ask the Axcellant team how your research can benefit from modern nuclear medicine procedures!


[i] Korde A, Mikolajczak R, Kolenc P, Bouziotis P, Westin H, Lauritzen M, Koole M, Herth MM, Bardiès M, Martins AF, Paulo A, Lyashchenko SK, Todde S, Nag S, Lamprou E, Abrunhosa A, Giammarile F, Decristoforo C. Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals. EJNMMI Radiopharm Chem. 2022 Jul 19;7(1):18. doi: 10.1186/s41181-022-00168-x. PMID: 35852679; PMCID: PMC9296747. https://pmc.ncbi.nlm.nih.gov/articles/PMC9296747/

[ii] Schwarz SW, Decristoforo C. US and EU radiopharmaceutical diagnostic and therapeutic nonclinical study requirements for clinical trials authorizations and marketing authorizations. EJNMMI Radiopharm Chem. 2019 May 22;4(1):10. doi: 10.1186/s41181-019-0059-2. PMID: 31659486; PMCID: PMC6529498. https://pmc.ncbi.nlm.nih.gov/articles/PMC6529498/

[iii] https://www.ema.europa.eu/en/radiopharmaceuticals-scientific-guideline

[iv] https://www.ema.europa.eu/en/non-clinical-requirements-radiopharmaceuticals-scientific-guideline

[v] https://www.ema.europa.eu/en/human-regulatory-overview

[vi] https://nucmed-guide.app

[vii] https://www.fda.gov/drugs/development-resources/medical-imaging-and-drug-development

[viii] https://www.fda.gov/drugs/development-approval-process-drugs

[ix] https://www.fda.gov/drugs/science-and-research-drugs/radioactive-drug-research-committee-rdrc-program#guidances

[x] https://www.nrc.gov

[xi] https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1782_web.pdf

[xii] https://www.iaea.org/resources/safety-standards/search

[xiii] https://www.iaea.org/resources/rpop

[xiv] https://link.springer.com/article/10.1007/s00259-022-05738-4


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