General issues in therapeutic nuclear medicine

» Overview of therapy with unsealed radionuclides

Radionuclide therapy is changing dynamically. Monoclonal antibody therapies for non-Hodgkins lymphoma using iodine-131; or imaging with indium-111, followed with yttrium-90 for the therapy are the next wave of a new generation of therapies. The basis of radionuclide therapy is simply the placement of the radionuclide in intimate contact with the target tissue. Particularly if short-range particle emitters are used, the absorbed dose to the target is very high compared to non-target tissues. The route of administration may also pose different radiation safety issues. Oral or intravenous administration of radionuclides is very common, but other methods of administration also exist, such as insertion directly into a body cavity.

Radionuclides are also gaining increasing importance by providing palliative and curative treatment in an increasing number of malignant diseases. Most radionuclides used in radionuclide therapy emit beta particles which have a low range of tissue penetration. A few emit auger electrons and alpha particles, and several also emit gamma rays and X-rays during their decay. The most successful metabolic radionuclide for thyroid therapy uses iodine-131 as the nuclide for the treatment of benign hyperthyroid conditions and thyroid carcinoma.

Pure beta particle emitters, with their lower penetration ability, deposit all their energy within the patient, ideally at the target site. From a radiation safety perspective, the radiation is limited to the patient, with minimal exposure to the public. When handling beta emitters, such as strontium-89, yttrium -90, or rhenium-188, radiation safety is primarily the safe handling of excreta and body fluids. However, when radionuclides also emit gamma rays - such as iodine-131 - or bremsstrahlung X-rays, exposure of the public to these photon emissions must also be considered.

The clinical use of phosporous-32 for palliation of painful bone metastases, highlights the changing role of radionuclide therapies. Although Phosphorous-32 has proven to be a good therapeutic modality in myeloproliferative diseases, the induction of secondary cancers such as leukaemia is problematic. Consequently, this therapy is being largely replaced by chemotherapy, which appears to have fewer adverse side effects. Conversely, palliative therapy of painful bone metastases, no longer responding to other therapies, is now widely practiced using strontium-89, rhenium-188, or samarium-153. Up to 70% of patients have a remission from pain, permitting them to reduce their intake of strong analgesics, which can last for several months.

Some of the more common radionuclides used for therapy and their main radiation emissions are found in the following table.

» Properties of some radionuclides used in nuclear medicine therapy
(Arranged in increasing order of mass number)

Nuclide Half-life Emission Eαmax
Eγ peak
32P 14.3 d β   1.71/0.695  
67Cu 2.58 d βγ   0.58 185
89Sr 50.5 d β   1.49/0.58  
90Y 2.67 d β   2.28/0.935  
125 I 60.0 d Auger      
131 I 8.04 d βγ   0.61/0.20 364
153Sm 1.95 d βγ   0.81/0.225 103
165Dy 2.33 h βγ   1.29/0.44 95
169Er 9.5 d β   0.34  
177Lu 6.71d βγ   0.497 208
186Re 3.77 d βγ   1.08/0.35 137
188Re 19.96h βγ   2.1 155
198Au 2.7 d βγ   0.96/0.31 411
211At 7.2 h α 6.8    
212Bi 1.0 h α 7.8    

»What to consider in case of external radiation and contamination by excretion of the radionuclide

In some cases, the patient is treated in hospital and allowed to go home immediately, but in other cases, the patient must be hospitalized until such time - considering the patient's family and the general public - as it is safe to allow discharge.

There are two radiation safety considerations that must be addressed: external radiation, and contamination by excretion of the radionuclide. The external radiation is simply related to the radionuclide used, and its emissions and half-life. Excretion however brings the possibility of contamination of the patient’s environment, and possible ingestion by other persons. These are considered separately for each therapy radiopharmaceutical in other modules.

Should the patient die following discharge, the problem of safe disposal of the body must be considered.

External radiation

The therapy patient is also a source of radiation. If the radionuclide used is a low energy beta emitter, then this radiation might not even be detectable. On the other hand, if a gamma emitter is of medium energy, then the radiation levels in the vicinity of the patient can be significant. At short distances, the inverse square law does not hold because the source is often distributed over a large area, so distance from the patient is not as effective as if it was a point source.

However, beyond about three meters distance, the inverse square law may be used.While the photon radiation exposure to family and caregivers is not significant in terms of future cancer risk, it should be kept as low as reasonably achievable (ALARA), especially for children and pregnant women.


The radiopharmaceuticals used may have a number of fates:

  • Total and permanent retention within the body. This is normally confined to particles which are trapped within a particular organ or system;
  • Partial trapping and retention of particles, with potential excretion of unbound radionuclide;
  • Partial trapping and retention of ionic compounds, with excretion of the remainder. 

The excretory pathways include:

  • Urine;
  • Faeces;
  • Saliva;
  • Sweat; 
  • Lacrimal fluid; 
  • Breast milk. 

Each pathway has different safety issues, and all can lead to contamination. In particular, the clearance rate of the radionuclide from the patient’s body can vary greatly, not only between radiopharmaceuticals, but also for the same radiopharmaceutical. The main route of excretion is generally through the kidneys leading to high concentrations of radionuclides in urine and discharge of radionuclides to the sanitary sewer. Some data are found in the table below.

Cross-contamination from patients to other persons is, however, generally less of a safety hazard than external radiation exposure. The likelihood of a significant intake by contamination is small, and poses an extremely low cancer risk.

Proportion of administered activity (until total decay) which is discharged to the sanitary sewer for some therapeutic radionuclides

Radionuclide and form For treatment of % discharged to sewer
Iodine-131 iodide Benign thyroid disease 54
Iodine-131 iodide Thyroid cancer 84-90
Iodine-131 MIBG Phaeochromocytoma 89
Phosphorous-32 phosphate Polcythaemia etc. 42
Strontium-89 chloride Bone metastases 92
Yttrium-90 colloid Arthritic joints 0

» Decision to hospitalize or discharge a patient

The IAEA Basic Safety Standards (BSS) and many national authorities apply limits to the retained activity level at which a patient may be released. These limits are based, in theory, on the estimated exposure to any member of the public remaining below a certain effective dose. This is either 1mSv (the dose limit for a member of the public), or 5 mSv, on the basis that - under International Commission on Radiological Protection (ICRP) and BSS recommendations - caregivers may receive higher doses than the public dose limit. Any restrictions should be based on the sensitive group of infants and children. The current BSS gives a guidance level for release of Iodine-131 patients (treated by any form of therapy), which is 1100 MBq. Other bodies such as the national bodies in Australia, Sweden and the United States, have their own guidelines. Most other guidelines are specific for Iodine-131 only. The BSS is undergoing revision.

The release limits vary widely, however, and take into account only the retained activity and no other factors such as self-absorption in the patient. The assumptions used in generating the limits often overestimate potential doses to caregivers and the public. The ICRP recommends that the decision should be determined on an individual basis, taking into account patients' pattern of contact with other people, their age and that of persons in the home environment, patients’ wishes, and local social and infrastructure issues. The cost of hospitalization, and radiation exposure of hospital staff should also be considered.

Estimation of exposure from external radiation is based not only on clearance from the body, but also on distance and exposure time. A profile of the time spent at certain distances from the patient can be developed for the spouse, and for other family members, which can then be used to estimate cumulative dose. Even these methods can significantly overestimate risk. If patients and caregivers follow simple radiation protection precautions, such as outlined later in this guideline, effective doses would rarely approach, let alone exceed, the 5 mSv level.

Experience shows that the occupational exposure to staff as a result of patients being held in hospital after therapy is generally very low or negligible. The major advantage of holding the patient is the control of the environment. The decision to release the patient is then based on the risk to others from this loss of control, balanced by the advantages to the patient and family. The BSS (para. II-9) states that “...the dose of any comforter or visitor of patients shall be constrained so that it is unlikely that this or her dose will exceed 5 mSv during the period of the patient’s diagnostic examination or treatment. The effective dose to children visiting patients who have ingested radioactive materials should be similarly constrained to less than 1 mSv.”

Sweden Australia
Rationale (adults) 5 mSv 3 mSv 25 μGy/hr @ 3 m
Iodine-131 5 mSv (adult) 600 MBq 600 MBq
Iridium-111 5 mSv (adult)   400 MBq
Phosphorous-32 5 mSv (adult) 1,200 MBq 1,200 MBq
Samarium-153 5 mSv (adult)   4,000 MBq
Strontium-89 5 mSv (adult)   300 MBq
Yttrium-90 5 mSv (adult) 1,200 MBq 4,000 MBq

Other iodine-131 release criteria

Country or
Release limit for
iodine-131 (MBq)
BSS 1,100 (guidance level)
European Thyroid Association 800
Japan 500 or <30 μSv/hr @ 1m
Germany 250 (based on 3.5 μSv/hr @ 2m)
Other EU Member States 95–800, mostly 400–600

Issues to be considered in release of therapy patients

Issue Hospitalization Release
Environment Controlled Less control
Occupational dose Present Reduced
Public exposure potential Less Present
Method of waste disposal Sewage or storage Sewage
Public exposure from waste Same unless stored Same
Monetary cost Significantly more Reduced
Psychological Significant Reduced
Patient death Exposure of funeral staff
Possible limitation of cremation

» How should I apply the principle of optimization in radionuclide therapy?

Optimizing radionuclide therapy procedures is somewhat different than in diagnostic nuclear medicine. In diagnostics, one wants to reach a balance between the administered activity and the image quality necessary for a correct diagnosis.

The radiation dose should be as low as reasonably achievable (ALARA), consistent with optimal image quality. In therapy, optimization requires an accurate, and precise prescribed dose to the target tissue or organ being treated in order to reach the desirable biological effect. Therefore, optimization means individual dose planning and calculation based on uptake measurements, the volume of the treated organ, and a correct determination of the amount of activity to administer. Individual dose planning for the treatment of thyroid diseases has only been used on a limited basis.

Often the thyroid is ablated, without precise or accurate dosimetry, simply ensuring that a minimum therapeutic dose has been delivered. Unlike external beam radiotherapy, much more work needs to be done to expand patient specific dosimetry for radionuclide therapy.

» Can I prescribe a radionuclide therapy to a pregnant woman?

As a rule, treatment of a pregnant woman with a radioactive substance is a medical decision based on consideration of radiation effects in addition to other factors. Sometimes the procedure may be deferred, a substitute treatment may be available, or the radionuclide therapy may be required to save her life. It is therefore essential that the potential absorbed dose and risk to the fetus should be estimated and provided to the referring physician and to the patient if requested.

» What principles should I apply in deciding for how long a patient should be hospitalized after radionuclide therapy?

The IAEA Safety Report Series No. 63 recommends that the decision should be determined on an individual basis, taking into account the patient’s pattern of contact with other people, their age and that of persons in the home environment, patients’ wishes, and local social and infrastructure issues. The cost of hospitalization and radiation exposure of hospital staff should also be considered.

The ICRP Publication 94 recommendations state that young children and infants, as well as visitors not engaged in direct care or comforting, should be treated as members of the public for radiological protection purposes (i.e., be subject to the public dose limit of 1 mSv/year). For individuals directly involved in comforting and caring, other than young children and infants, a dose constraint of 5 mSv per episode (i.e., for the duration of a given release after therapy) is reasonable. The constraint needs to be used flexibly. For example, higher doses may well be appropriate for parents of very sick children.

A profile of the time spent at certain distances from the patient can be developed for the spouse, and for other family members, which can then be used to estimate cumulative dose. If patients and caregivers then follow simple radiation protection precautions, including the use of personnel dosimeters, radiation doses should rarely approach the dose constraints. See section on the decision to discharge the patient.

The decision should be taken together with a medical physicist or radiation protection officer.

» What do different countries require for discharge of the patient?

There is no standardization among countries for discharge or release criteria. Some use a fixed radioactivity level, some use a dose rate from the patient, and others use an estimated dose to family members following return home. See section on the decision to discharge the patient. Most other guidelines are specific for iodine-131 only.

» What are the radiation risks to the public?

The public can be exposed to radiation from a radionuclide therapy patient as:

  • external radiation emitted from the patient, when in close contact (such as on public transport);
  • internal contamination from radioactive body fluids;
  • exposure through environmental pathways including sewage, discharges to waterways, or cremation of bodies. 

In the case of the public, the normal dose limit of 1 mSv/year applies. Exposure of the public from radionuclide therapy is often caused from the external exposure, with internal contamination and environmental exposures contributing little, if any exposure. Specific discharge guidelines often provide the necessary information for a specific radionuclide and therapy.

» The patient has to use public transport regularly. What precautions should s/he take?

If travel times sitting next to a person administered with radiopharmaceutical are less than a few hours, radionuclide therapy patients rarely present a hazard, except for iodine-131 therapy when doses over 1000 MBq are administered. For example, take the case of a patient treated with 600 MBq of iodine-131 for hyperthyroidism. One hour of travel daily on public transport in the first week after therapy, and nine hours per day in the second week, next to the same person, will result in an effective dose of <1 mSv-1.

For family members, the suggested travel time using public transport with hyperthyroid treatment patients is seven hours per day for the first week and 24 hours per day for the second week, to restrict the effective dose constraint of 5 mSv per episode - in other words, travel restrictions are often not necessary.

» Will the radioactivity from the patient harm the environment?

The main radionuclide discharged into the environment following radionuclide therapy is radioiodine (iodine-131). Due to the half-life of 8 days, iodine-131 may be detected in small amounts in the general environment after medical use. However, because of the high degree of dilution in a planned facility and dispersion when mixed with normal waste discharges, and the long period of time required for this activity to be returned to the ecosystem, the environmental impact may be minimal and often not even detectable.

Some countries require short-term storage of hospital waste (usually urine only) containing radionuclides from hospitalized therapy patients until the activity has reached a particular level; however, the ICRP does not specifically require this.

For radionuclides used in bone pain palliation, it is suggested in this guideline that where the therapy is given to an outpatient, the patient should empty the bladder at least once before leaving the hospital. If the social system and infrastructure in a country increases the probability of higher exposure from discharged patients, it may be necessary to hospitalize the patient (if an outpatient therapy), or extend the normal hospitalization time.

» The patient is undergoing regular haemodialysis. Is this a risk?

There have been reports of significant contamination of dialysis machines. In cases where there may be slight contamination from iodine-131 of disposable items such as lines and waste bags, these may simply be allowed to decay a few half lives by storing them in a shielded and secure location. Otherwise, haemodialysis will not require additional precautions.

» How is the radioactive waste from the patient disposed of, and does it pose a risk?

The main concern is radioactive excreta - urine and faeces. The specific therapy discharge guidelines will recommend that excreted radioactivity levels be low enough such that the public dose limits would not be exceeded. In addition, the ICRP does not recommend that urine from therapy patients be stored - a procedure which has minimal benefit, and can even lead to higher exposures due to the additional and unnecessary handling of the urine. The IAEA Safety Report 63 also accepts this advice. It is safer and simpler to simply discharge the urine into the sewer system. The inherent shielding, dilution, and eventual decay will reduce the activity to minimal levels.

Other wastes such as dressings will usually end up in landfill or incinerators. Again, by following recommended specific therapy discharge guidelines, any released activity will be extremely low and negligible.
Solid waste from the patient's stay in hospital is a different matter, and is normally incinerated at high temperature along with other biological waste (which does not pose a contamination problem). It may also be held for a period of time so that the radioactive decay reduces the activity to an acceptable level. The relatively short half lives of therapeutic radionuclides make this a manageable problem.