Joint EANM, SNMMI, and IAEA Enabling Guide: How to Set up a Theranostics Center

REGULATORY, LOGISTICAL AND TECHNICAL CONSIDERATIONS

The design, construction and subsequent operation of a theranostics service has to be guided by the fundamentals of radiation protection established by the appropriate regulatory agencies. In Europe, the International Atomic Energy Agency (IAEA) through the International Basic Safety Standards (BSS) (5) are a set of consensus requirements derived from knowledge of radiation biology and radiation protection, respectively (6). In the USA, the Nuclear Regulatory Commission (NRC) governs safety standards and delegates’ responsibilities to specific states (Agreement States) in many instances. The European Commission Directive 2013/59/EURATOM is a legal act that establishes the recommendations and requirements of the BSS and ICRP for EU countries, which have been transposed into national law by the Member States. Sections 2 and 3 of the BSS specify that requirements that apply to all existing and planned exposure situations must be considered when establishing and operating a theranostics center.

The BSS requires that legal entities apply to the regulatory authority for a license. Therefore, the regulatory basis for operating a theranostics center is a radioactive material license (RAM), in accordance with the national regulations and laws governing the handling of radioactive materials for medical applications, as defined in ICRP Publication 105 (7). This must cover all aspects of both diagnostic and therapeutic use of radiopharmaceuticals. Prerequisites for applying for a RAM license include the existence of adequate infrastructure, sufficient personnel (including trained physicians, technologists, nursing staff, a Radiation Safety Officer (RSO), a Medical Physics Expert (MPE)), sufficient means of radiation protection, and processes for discharge management of treated patients and handling of radioactive waste and sewage. To this end, several requirements must be met, depending on the respective spectrum of diagnostics and therapies applied and the radiopharmaceuticals used. In the US, regulations differ but require a suitable radiation license and appropriately qualified authorized users to allow administration of the radiopharmaceutical therapies.

RADIONUCLIDES AND RADIOPHARMACEUTICALS USED

A commonly used theranostic pair is gallium-68 (⁶⁸Ga) for PET/CT diagnostics and ¹⁷⁷Lu for therapy. In the US, [⁶⁴Cu]⁶⁴Cu-DOTA-TATE is commonly used in addition to [⁶⁸Ga]⁶⁸Ga-DOTAT-TATE or DOTA-TOC. However, ⁹⁰Y is also occasionally therapeutically, as are fluorine-18 (¹⁸F)- and technetium-99 m (^99mTc)-labeled diagnostic compounds. Table 1 summarizes the main properties of these radionuclides.

With ¹⁷⁷Lu, attention must be paid to the underlying manufacturing pathway, which may result in unwanted long-lived accompanying nuclides that require special consideration in terms of storage and disposal of waste depending on local regulations. ¹⁷⁷Lu is made either by direct neutron irradiation of ¹⁷⁶Lu targets (¹⁷⁶Lu (n,γ) reaction) or indirectly as a decay product of the neutron irradiation of ytterbium-176 (¹⁷⁶Yb (n,γ) reaction), which produces ¹⁷⁷Yb that decays to ¹⁷⁷Lu. In the indirect reaction, no long-lived contaminants are created. However, in the direct reaction, small quantities of metastable lutetium-177 (^177mLu) with a half-life of 161 d may be present (7). In this case, ^177mLu may account for approximately 0.02% of the total amount of ¹⁷⁷Lu in the final radiopharmaceutical. ⁶⁸Ga may either be obtained from a radionuclide generator (⁶⁸Ge/⁶⁸Ga-generator) or produced by proton irradiation of zinc-68 (⁶⁸Zn(p,n)⁶⁸Ga). The different production pathways of the radionuclides are associated with different radionuclidic impurities that must be taken into account, i.e. germanium-68 and gallium-67, respectively (8). The ⁹⁰Y currently available for radiolabeling is of high radionuclidic purity with no relevant amounts of accompanying nuclides (9). Long-lived radioactive contaminants may require specific regulatory attention.

RADIATION PROTECTION, SHIELDING

Shielding of syringes and vials, as well as in some jurisdictions, waste and storage containers, is an important aspect of reducing external exposure among staff, the public and patients. After administration of the radiopharmaceutical, it may be necessary (mainly in Europe, and in some cases in the US depending on exposure rates) to isolate the patient from other persons, either within the hospital or in the public domain. The type of radiation emitted from the theranostics compound will dictate the extent of shielding required. This can vary from PMMA (polymethyl metacrylate) storage boxes for vials and waste containers, lead pots and tungsten syringe shields, to concrete waste bunkers or lead-lined treatment rooms. This infrastructure must be prepared according to local regulation and must be in place before any activity involving radiation is carried out. Appropriateness of the control measures must also be demonstrated, usually in the form of a written radiation risk assessment that considers radiation protection of both employees and patients. Established risk analysis methods such as failure mode and effects analysis (FMEA) or fault tree analysis (FTA) should be used for this purpose. Compliance with NRC and/or state radiation safety regulations is required in the US.

STORAGE OF RADIOPHARMACEUTICALS

Radiopharmaceuticals must be stored in a safe, secure, and environmentally appropriate (such as refrigerated or frozen) place to which only the licensee and appropriate staff may have access. In addition, provisions for the safe storage and custody of radioactive materials must be in place, including protection against theft, fire, and chemicals. Transport and movement of radioactive materials to, from, and within the hospital must be carefully documented so that any radioactive material can be tracked from source to final use and disposal.

ADMINISTRATION OF RADIOPHARMACEUTICALS

Accurate quantification of the radioactivity administered to the patient is the first step of the radiopharmaceutical administration and traceability chain. A radionuclide calibrator measures the activity and cross-calibrates other equipment. It is therefore essential to ensure that calibration is traceable to primary standards when these are available (10–12).

A well-documented program for quality assurance (QA) and quality control (QC) is essential to ensure the dependable performance of safe, accurate and reproducible equipment operation and the appropriate clinical administration of radiopharmaceuticals (10,13,14). Following installation of any new instrument, acceptance testing must confirm that the system meets the performance specifications and to provide a baseline for comparison during routine QC. The type and frequency of QC tests should follow national guidelines.

The theranostics compounds can be administered in several ways: Adequate shielding must be ascertained to avoid undesirable beta and gamma irradiation and to minimize the risk of contamination, e.g., by using hybrid shielding consisting of layers of PMMA and lead/tungsten, which results in attenuation of both beta and gamma radiation and minimizes the occurrence of bremsstrahlung. A syringe is prepared with the therapeutic agent, and the qualified operator administers the drug via correctly placed and patent intravenous access. This is followed by flushing with saline. This method is particularly used for drugs such as PSMA ligands, which do not require specific administration as a bolus. Alternatively, the syringe content can be administered via perfusor or injection pump. To minimize staff radiation exposure it is recommended to use automatic dispensing and semi- or fully automated infusion pumps for the administration of the radiopharmaceuticals.

RADIOACTIVE WASTE

Storage for decay is essential for the clearance of radioactive waste containing short-lived radioisotopes, with a half-life of less than 100 d. “Clearance is the removal of radioactive material from regulatory control provided that the radionuclide concentrations are below specific clearance levels” (12).

Waste may be stored for decay and subsequent discharge in a locked, ventilated and properly demarcated room. It is recommended to segregate radionuclides according to the expected time required for their decay (e.g., initial activity and physical half-life). For example, the shorter lived waste from PET/CT diagnostics (syringes, swabs, vials, etc.) should be separated from that of the longer lived radionuclides used for the therapy. There should also be sufficient space in these rooms for interim storage of potentially contaminated items (e.g., patient clothing, patient diapers, perfusors, etc.). The origin of the waste should be recorded to ensure proper identification.

Disposal of aqueous radioactive wastes must strictly follow the recommendations set out in the national regulations. These may allow a limited amount of highly diluted wastewater to be disposed of into the public sewage system or require specific processing such as filtration and/or specific storage systems before release. Local regulatory authorities may also additionally require the facility to regularly assess the environmental and radiologic impact of radiation work being undertaken.

If long-lived contaminants such as ^177mLu (t1/2 = 160 d) are present in the radiopharmaceutical, the waste (e.g., vials, cannula, infusion lines, swabs, etc.) should be stored separately from other waste until the time limit for disposal according to national law is reached. Specific attention must be paid to isolation, storage and disposal of biohazardous and radioactive waste which may contain patient fluids. Potential contamination of liquid waste (i.e., excreta) with ^177mLu must also be considered, and any wastewater treatment or storage facilities used—if applicable—must be inspected for capacity and compliance with regulatory limits. Installation of separate toilets for patients treated with theranostics compounds potentially containing ^177mLu is also an option.

RELEASE OF PATIENTS AFTER TREATMENT

Prior to injection of a radioactive substance, radiation safety guidance should be given to the patient and family (where applicable) regarding rules of conduct to reduce the potential radiation exposure to others. Release of patients after diagnostic procedures does not require extensive or any (USA) measures, since the physical and effective half-life of radiotracers involved is usually only a few hours. With ⁶⁸Ga-, ⁶⁴Cu-, or ¹⁸F-based tracers it is therefore usually sufficient to restrict direct contact between the patient and vulnerable individuals (pregnant women, children) during the hours immediately after patient release. In the US, no or limited radiation specific discharge instructions are given following diagnostic procedures. The situation is somewhat different for patient discharged after therapeutic administrations, as the activity levels here are significantly higher. ICRP Publication 94 (15,16) and IAEA Safety Report no. 63 (17) comment on the release of patients after radionuclide therapy. A dose limit of 1 mSv/y for the public and a dose constraint of 5 mSv/episode for caregivers (a family member or paid helper who regularly looks after a child or a sick, elderly, or disabled person) have been proposed as acceptable limits. However, in many countries there are different limits and specifications that must be followed after therapeutic administration of radionuclides. In [¹⁷⁷Lu]Lu-PSMA-617 therapy, for instance, patients are typically treated with an activity of 7.4 GBq and the initial dose rate from the patient after the injection is in the order of 50 μSv/h at a distance of 1 m. If, as in many countries, a dose rate threshold of 30 μSv/h at a distance of 1 m is used as release criterion, the therapy can be applied as an outpatient treatment and patients can return home within 6 h of administration (18). Consideration must be taken when more than one radionuclide therapy per year is administered. For example, if a patient is treated with 6 cycles of PSMA-targeted therapy per year, the cumulative exposure received by the family members, the caregivers and the public must be considered. In this case, exposure to members of the public that the patient has frequent contact with (such as family members, children or coworkers) should be kept below one sixth of the annual limit after each cycle. The same considerations can be applied to [¹⁷⁷Lu]Lu-DOTATATE therapies.

For both therapies, the high excretion rate in the first hours after therapy administration must be considered: after 4 h, approximately 50% of the activity may be renally excreted (19,20). To be compliant with the dose limits, a system needs to be established to measure or estimate activity in patients before discharge and calculate the exposure that members of the household and public may receive (European standards do not apply in other parts of the world). The result should be recorded. One method of estimating the acceptable activity of radiopharmaceuticals in patients upon discharge from hospital is to calculate the time integral of the ambient equivalent dose rate and compare it with the dose limits. Direct measurement of patient activity before discharge is commonly performed and can be used as a patient-specific guide to minimize radiation exposure to caregivers and the general public. The patient should be given written instructions on precautions for the first few days after discharge. In particular, contact with pregnant women and small children should be avoided. Special attention should be given to the risk of contamination via urine, especially in the case of incontinent patients and children. In some cases, it may be appropriate to mandate hospital isolation due to this risk, even if the external dose rate is deemed adequately low. In some countries, including Germany, Austria and Italy, hospitalization is in any case mandatory following radionuclide therapy.

HANDLING OF DECEASED PERSONS

Despite careful patient selection, death of patients, while receiving therapy or soon after, could happen. Such cases could increase as the use of radiopharmaceutical treatments becomes more widely used. If such situations arise, appropriate measures must be taken to handle the corpse. This includes restricted access to the room occupied by the deceased until a proper decontamination and survey have been completed. Radioactive corpses must be identified as a potential hazard using proper identifiers. In case of leakage of radioactive substances, a body bag is needed. In addition, surveillance may be needed in all stages of disposal (17). None of this however is currently required in the US but careful discussions are commonly held with funeral homes regarding safe handling of patients who have died soon after receiving a radiopharmaceutical therapy.

Handling (preparation for burial or cremation) of a body containing significant radioactivity must be performed under the supervision of a radiation protection officer (17). Depending on the national regulations, cremation may be postponed for several days or even weeks. Autopsy is not advisable in such cases and must be kept to a minimum. In consultation with the radiation protection officer, all necessary radiation protection and decontamination measures must be undertaken for personnel, instruments and the workplace.

TREATMENT PLANNING, OPTIMIZATION AND VERIFICATION

Council Directive 2013/59/Euratom calls for the planning, optimization and verification of all radiotherapy exposures in the geographical areas of the EU. The EANM recently provided guidance on how to interpret the Directive’s statements for NM treatments (21). Theranostics procedures are the epitome of such exposures, allowing the appropriateness of therapy to be determined via companion diagnostic imaging, followed by post-administration therapy imaging for treatment verification, followed by further diagnostic response imaging. ⁶⁸Ga- is generally accepted as the favored diagnostic companion for ¹⁷⁷Lu-based therapies although copper-64 (⁶⁴Cu) is seeing increased application in some settings. Most countries in the EU, North America and the Far East show a fairly high density of PET centers, that is, at least 1/million (22). The short half-life of ⁶⁸Ga can make transport to centers difficult unless the production site is a short distance away or production is carried out within an in-house radiopharmacy facility. With the emerging availability of licensed kits for ⁶⁸Ga-labeled tracers, the clinical availability of these compounds and the longer lived tracers such as ⁶⁴Cu will increase as well. Considering the many advantages of PET/CT imaging as a companion diagnostic tool, all efforts should be made to equip the countries still lacking so that equal access to therapies can be achieved, as highlighted by the Lancet Oncology Commission on Medical Imaging and Nuclear Medicine (22). Scaling up access of imaging, treatment, and care quality will produce substantial health and economic benefits, and avert millions of death, but will require initial investment before a return is observed (22).

The complexity of the task and the resources required to implement theranostics will vary depending on the respective radiopharmaceutical, application and desired clinical end-point (23). Commercial software applications are now available, some of which have FDA/EMA approval and are intended to perform dosimetric evaluation (24). However, in many centers, software developed in-house is still widely used and remains a valuable option for research purposes and post-therapy dosimetry.

Dosimetry calculations require measurements of the distribution of activity in the targets of interest at different time-points to determine the time-integrated activity (25,26). Methods requiring less resourcing include whole-body, blood and bone marrow dosimetry, which use external probe measurements of the activity in a tissue biopsy, blood sample or whole body (27). The number and frequency of activity measurements require careful consideration and should match the desired biological and clinical endpoint. For wider implementation, there is growing interest in minimizing the number of imaging sessions while having a sufficient level of accuracy to achieve the desired treatment outcome and reduce patient burden and hospital costs. Nearly all radiopharmaceutical therapies approved in the US do not require dosimetry as a part of the product labeling.

Publications on general principles and practice of PET/CT imaging as well as information about the EARL accreditation program for the harmonization of ¹⁸F, ⁶⁸Ga and ⁸⁹Zr imaging are provided by the EANM (28,29). The EANM guidelines provide recommendations on setting up quantitative SPECT/CT imaging with examples of potential clinical applications and include details on scanner calibration, image acquisition parameters, and reconstruction and correction methods (30,31). The EANM also provides general guidance on documenting and reporting dosimetry data to facilitate the reproducibility of results (32), as well as a detailed methodology on the evaluation and calculation of uncertainties in absorbed dose calculations (33). Guidance on logistical and technical considerations when developing quantitative imaging and dosimetry protocols is available for ¹³¹I (34–38), ¹⁷⁷Lu (39–41), ⁹⁰Y (42), ²²³Ra (43–45). The Radiological Society of North America QIBA profiles can inform PET and SPECT applications as can use of the SNMMI Clinical Trials Network Phantoms.

MEDICAL CONSIDERATIONS AND REFLECTIONS

Application of radionuclide therapies requires the involvement and coordination of multiple stakeholders—inter- but also intra-professionally. Whereas in regular patient care the treating physician is also the referring physician, patients undergoing radionuclide therapy are typically followed by clinicians who are not nuclear medicine physicians. In the case of prostate cancer patients, the majority are seen and followed by urologists and medical oncologists. However, radioligand therapies are delivered by authorized users, most typically within nuclear medicine departments. Accordingly, coordination and communication with the treating physician are of utmost importance, especially as the indication of radioligand therapies must be appropriately sequenced in the disease journey of a patient. An active presence and participation of nuclear medicine specialists in the multidisciplinary team is mandatory to ensure acceptance and awareness of radioligand therapies. While in the past our contribution to multidisciplinary teams was often limited to presenting diagnostic images, we now must play a more active role in providing our expertise for potential treatment. Overall, a proactive approach promoting theranostics methods will facilitate the adoption and acceptance of our field by our clinical colleagues. This role change also needs to be reflected in the training of junior doctors and the continued education of board-certified nuclear medicine specialists.

INTEGRATED CARE

The success of a theranostic center highly depends on the level of integration within an oncologic practice. Indeed both diagnostic imaging as well as radioligand therapy have to be embedded within the oncologic workflows to facilitate access to the patient flow controlling clinicians. Not surprisingly the currently most successful theranostic centers are embedded in strong cancer centers focusing on neuroendocrine tumors and prostate cancer. Accordingly in anticipation of an ever growing number of theranostic indications, a close collaboration with all clinical domains managing cancer patients is very important.

INTRA-PROFESSIONAL STAKEHOLDERS

Apart from the interprofessional complexity of theranostics, it is also important to address the multiple specialties and skill sets involved in the successful operation of a theranostics center. In addition to medical expertise including both physicians and well-trained support staff such as nurses, the administration of either commercially or locally produced theranostics agents requires the involvement of medical physicists, radiochemists/radiopharmacists and radiation safety experts. Whereas many of the skill sets required for theranostics resemble those needed for diagnostic nuclear medicine procedures, the higher activity levels needed for therapy, the different radionuclides involved and the multiple steps in the process, from validating the indication to delivering the radiopharmaceutical, often calls for a significantly higher degree of knowledge but also requires more time. The less infrastructure and local expertise that is already in place, the more demanding the transition to a state-of-the-art theranostics center will be. Needless to say, the adjustments required from a center with experience in delivering high-activity radioiodine therapies will be less onerous than those for a site currently only dealing with diagnostic outpatient procedures or ²²³Ra outpatient treatments.

TRAINING AND EDUCATION

The expected surge in demand for theranostics centers entails numerous challenges. Accessibility and availability of a skilled, well-trained workforce represent one of the greatest unmet needs, alongside upscaling of the healthcare system to accommodate the expected demand for radionuclide therapies. Training and education of existing board-certified nuclear medicine specialists is of high importance, as is the incorporation of radionuclide therapy and the concept of theranostics into the curricula of the ongoing training programs for junior doctors. Besides learning how to apply radionuclide therapy, understand the right timing for theranostics and the alternative treatments that could be available, deal with typical toxicity profiles and manage the corresponding side effects, there is also an overall shift toward being more actively involved in patient treatment. While cross-training in radiology is helpful for the diagnostic nuclear medicine procedures, the spectrum of radionuclide therapies rather demands a profound expertise in internal medicine, oncology and/or urology. Experienced theranostics centers in countries such as The Netherlands, Switzerland, Germany, the United Kingdom and others should accommodate interested nuclear medicine specialists from elsewhere to acquaint them with the application of radionuclide therapies. In the US, radiation oncologists can become authorized users, but current training for such practitioners in radiopharmaceutical therapy is often quite limited as their focus is external beam therapy in most centers. Practical training of nuclear medicine technologists is also needed, along with continuous education programs for the development of skills and dissemination of best practice principles. The success of theranostics and the independence of nuclear medicine are directly dependent on our success in meeting patient demand. In parallel, the introduction of theranostics fellowships mutually accepted by national and international nuclear medicine and clinical societies needs to be pursued. Nuclear medicine physicians who have attained expertise in theranostics will in turn be able to inform the clinicians about all specific aspects of the new treatments with radionuclides. The goal is for medical oncologists and urologists to reach a similar level of comfort with referring patients for these treatments as that reached by clinicians dealing with clinical indications of ¹³¹I in care of thyroid diseases. In the US, the SNMMI has endorsed the usage of the term “nuclear oncologist” to refer to nuclear medicine physicians with special expertise in treating cancer patients with targeted radiopharmaceuticals. This term associated with appropriate training and experience may better reflect the critical role of the oncology focused nuclear medicine physician and warrants further use.

LESSONS LEARNT

Based on our experience, the most important aspect in preparation for the likely surge in theranostics treatments is to seek advice and experience from centers already actively involved in such treatments. Of the lessons learnt, by far the most important is that careful preparation and planning are key to successful implementation.

With an increase in the breadth of theranostics services being delivered comes a larger variety of patients with a wider range of comorbidities and potential complications in safely delivering a radionuclide therapy. Historically, with I-131 thyroid treatments we have been privileged in treating relatively young and healthy patients. While Xofigo® ([²²³Ra]RaCl₂) treatments brought in an older, frailer population, the reduced radiation risks from the alpha-emitter meant that therapies could still be safely delivered in high numbers as an outpatient service in most countries.

PSMA ligand treatments, particularly when radiolabeled with Lu-177, do not necessarily benefit from the same logistical advantages, and thought should be given to the potential complications that could arise from treating such patients. Most notable, from experience, is the increase in the number of patients presenting with some form of lower urinary tract symptom. The degree of incontinence will vary from patient to patient and may be controllable through the wearing of absorbent diapers, or through external, self-inserted or semipermanent catheterization. Artificial sphincters and other interventions have also been observed. For a treatment where the primary form of excretion is via the urinary system, this aspect should not be overlooked. A thorough and clear patient history is required so that control measures can be put in place to deal with these complications and there are no surprises on the day of therapy and once the patient returns home.

Consideration should also be given to the patient after treatment. Responsibility for the radiation and potential risks that may occur to the patient, the public and the environment do not stop after the patient has left the hospital. Contingency planning is required to deal with the unexpected, be it disease, treatment, or unrelated emergency care. Examples that have been experienced include blood transfusions for anemia, orthopedic surgical interventions and even patient death (46). It should be recognized that theranostics treatments will impact surrounding and local hospitals in addition to those delivering the radionuclide therapy. It is also likely that the receiving center and staff will not have the expert knowledge or facilities to deal with radioactive patients or potentially will not possess the required licenses to administer radioactivity or to handle such a patient on site. Good communication and coordination between centers are therefore paramount.

With the expected demand for treatments, outpatient or day case administrations are appealing with a view to increasing patient throughput. However, patient preparation and treatment delivery should not be rushed. Even in centers and countries where treatments can be delivered as a day case, preparations should be in place to respond to delays and contingency plans should be in place to admit the patient overnight, should the need arise. Until the number of theranostics centers increases, extended patient travel time can be expected as current centers cover a wider geographical area. Radiation restrictions during this period should be considered and guidance given as to whether it is more appropriate for the patient to stay in local accommodation rather than undertake a lengthy journey home immediately after therapy.

PROVIDING POINTS OF CONTACT

Promoting theranostics and the scale-up of sites providing access to radionuclide therapy is a joint effort involving multiple professional societies such as EANM and SNMMI, international agencies such as IAEA, but also multiple industry-driven initiatives. A very solid source of information are procedural guidelines promoting the use of innovative diagnostic and therapeutic radionuclides such as [⁶⁸Ga]Ga-PSMA ligands (47), [¹⁷⁷Lu]Lu-PSMA ligands (48), [²²³Ra]RaCl₂ (49), and on a more general level peptide receptor radionuclide therapy (31), among many others. The leading professional societies generally attempt to provide early guidance on how to use novel theranostics, even in cases where clinical evidence is still lacking. For detailed review, both EANM and SNMMI provide direct access to an overview of procedural guidelines (46,50). In addition, several EANM committees, such as the EANM Oncology & Theranostics Committee, or the SNMMI Therapy Centre of Excellence serve as an entry point for individuals requesting assistance or information on how to promote theranostics at local level. More recently, multiple joint initiatives have been launched, paving the way for an understanding of theranostics within the oncologic community and facilitating the increased exchange between clinicians and nuclear medicine experts. A pioneering example of this is the joint ESMO/EANM initiative offering advanced courses on diagnostic and therapeutic applications of nuclear medicine in oncology. Additional industry-driven initiatives have recently been announced and will also provide very valuable sources of education and training.

SUMMARY

The expansion of theranostics applications beyond thyroid cancer and neuroendocrine tumors to a higher-incidence disease such as prostate cancer is triggering the up-scaling of existing and new theranostics centers. This guide establishes an overarching framework helping practitioners to understand what is needed and required to set up a theranostics center. Despite a widely varying regulatory, financial and medical landscape, the nuclear medicine community will doubtless prove capable of responding to the expanding practice in this field. The era of theranostics offers a great opportunity to improve patient care, and theranostics will become a mainstay of personalized cancer treatment. As a community we have the experience and facilities to deliver, with careful preparation and collaboration we will see expansion, and will be ready and able to respond to the demand placed on us as theranostics continues to develop.

DECLARATIONS

Informed consent: This manuscript does not contain proprietary human data; accordingly an informed consent is not applicable.

Conflicts of interest: KH reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, all outside the submitted work. LG reports personal fees from Roche Diagnostics and SNIBE for advisory board participation, and research support from Roche Diagnostics., all outside the submitted work. AMDB is supported by the National Measurement System of the UK Department for Business, Energy and Industrial Strategy. RLW has research contracts from Siemens, Bayer, Actinium Pharmaceuticals, and serves (with compensation) on the scientific advisory boards of Seno Medical and Clarity Pharmaceuticals. HJ serves on the advisory board of Radiomedix, is a consultant to Bayer and Blue Earth Diagnostics, an investigator for ImaginAb, and on the speaker’s bureau of Lantheus. MG reports fee for speakers bureau of Novartis, Blue Earth and Ionetix (not active currently). The remaining authors have no relevant conflict of interest to declare with regards to this comment.

Research involving human participants and/or animals: This manuscript does not contain proprietary research involving neither humans nor animals.

Liability: This guideline summarizes the views of the co-authoring EANM Committee members, SNMMI representatives and IAEA co-authors. It reflects recommendations for which the EANM, the SNMMI and the IAEA cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.