Recommended citation
ICRP, 2019. Radiological protection in therapy with radiopharmaceuticals. ICRP Publication 140. Ann. ICRP 48(1).
Authors on behalf of ICRP
Y. Yonekura, S. Mattsson, G. Flux, W.E. Bolch, L.T. Dauer, D.R. Fisher, M. Lassmann, S. Palm, M. Hosono, M. Doruff, C. Divgi, P. Zanzonico
Abstract - Radiopharmaceuticals are increasingly used for the treatment of various cancers with novel radionuclides, compounds, tracer molecules, and administration techniques. The goal of radiation therapy, including therapy with radiopharmaceuticals, is to optimise the relationship between tumour control probability and potential complications in normal organs and tissues. Essential to this optimisation is the ability to quantify the radiation doses delivered to both tumours and normal tissues. This publication provides an overview of therapeutic procedures and a framework for calculating radiation doses for various treatment approaches. In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by radiopharmaceutical uptake, retention in and clearance from the various organs and tissues of the body, together with radionuclide physical half-life. Biokinetic parameters are determined by direct measurements made using techniques that vary in complexity. For treatment planning, absorbed dose calculations are usually performed prior to therapy using a trace-labelled diagnostic administration, or retrospective dosimetry may be performed on the basis of the activity already administered following each therapeutic administration. Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes; these analyses show the reliability and quality of absorbed dose calculations. Effective dose can provide an approximate measure of lifetime risk of detriment attributable to the stochastic effects of radiation exposure, principally cancer, but effective dose does not predict future cancer incidence for an individual and does not apply to shortterm deterministic effects associated with radiopharmaceutical therapy. Accident prevention in radiation therapy should be an integral part of the design of facilities, equipment, and administration procedures. Minimisation of staff exposures includes consideration of equipment design, proper shielding and handling of sources, and personal protective equipment and tools, as well as education and training to promote awareness and engagement in radiological protection. The decision to hold or release a patient after radiopharmaceutical therapy should account for potential radiation dose to members of the public and carers that may result from residual radioactivity in the patient. In these situations, specific radiological protection guidance should be provided to patients and carers.
© 2019 ICRP. Published by SAGE.
Keywords: Radiopharmaceutical therapy; Radionuclide; Dose estimation; Radiological protection.
Key Points
Treatment with radiopharmaceuticals requires administration protocols that justify and optimise the treatment. Individual absorbed dose estimates should be performed for treatment planning and for post administration verification of doses to tumours and normal tissues.
Special consideration should be given to pregnant women and children exposed to ionising radiation. Pregnancy is usually contraindicated in radiopharmaceutical therapy. Breast feeding should be discontinued in patients receiving radiopharmaceutical therapy.
Radiation sources used in radiopharmaceutical therapy can contribute to exposures to medical personnel and others who may spend time within or adjacent to rooms that contain such sources. Meaningful radiation dose reduction and contamination control can be achieved through the use of appropriate procedures, and facility and room design, including shielding where appropriate, as well as education and training to promote awareness and engagement in radiological protection. Accident prevention and review of safe practices in radiopharmaceutical therapy should be an integral part of the design of facilities, equipment, and administration procedures.
Medical practitioners should provide all necessary medical care consistent with the radiological protection principles of justification and optimisation. Radiological protection actions should not prevent or delay life-saving medical procedures or surgery in the event that they may be required for medical care. Staff should be informed and trained with respect to patient radiation levels.
The decision to hospitalise or release a patient after therapy should be made based on existing guidance and regulations, as well as on the individual patient’s situation, considering factors such as the residual activity in the patient, the patient’s wishes, and family considerations (particularly the presence of children or pregnant family members). Information to guide radiological protection at home should be provided to patients and carers.
Executive Summary
(235) The increasing use of radiopharmaceuticals for cancer therapy promises new treatment options for patients. The challenge for all radiation therapy is to optimise the ability to treat cancer successfully (tumour control probability) against potential adverse effects and normal tissue complications. Radiopharmaceutical therapy provides opportunities to maximise the therapeutic index, a measure of both efficacy and safety.
(236) In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by the individual patient biokinetics (uptake, retention, and clearance), which may vary widely from one patient to another. Measurements of radiopharmaceutical biokinetics provide essential information needed for internal dose assessment.
(237) Due to biokinetic differences, personalised dosimetry must be performed for each patient. In principle, a fully personalised approach based on patient-specific measurements can ensure treatment with an appropriate activity level without exceeding normal organ and tissue toxicity thresholds.
(238) Special consideration should be given to pregnant women. Pregnancy is contraindicated in radiopharmaceutical therapy, unless the therapy is life-saving. Female patients should be advised that breast feeding is also contraindicated after therapeutic administration of radionuclides.
(239) In addition to the patients treated with radiopharmaceutical therapy, the people at risk of exposure include hospital staff, members of the patient’s family (including children), carers, neighbours, and the general public. These risks can be effectively managed and mitigated with well-trained staff, appropriate facilities, and the use of patient-specific radiation safety precaution instructions.
(240) Radiological protection measures to minimise medical staff exposures include use of proper equipment and shielding, safe handling of radioactive sources, use of personal protective equipment and tools, and education and training for commitment to improve awareness and engagement in safety practice. Individual monitoring of the worker doses and extremity doses must be considered during the management of radiopharmaceutical therapy patients, and during preparation and administration of the radiopharmaceuticals.
(241) Medical practitioners should provide all necessary medical care consistent with patient safety and appropriate medical management. Radiological protection considerations should not prevent or delay life-saving operations in the event that surgery is required. Staff should be informed when a patient may present a source of radiation exposure. Training should help the staff to put risk concerns into proper perspective.
(242) The decision to hospitalise or release a patient after therapy should be made on an individual basis, considering factors such as the residual activity in the patient and existing guidance and regulations. Specific radiological protection precautions should be provided to patients and carers.
(243) Prevention of medical errors with radiopharmaceuticals should be an integral part of the design of equipment and premises, and of the working procedures.
Technical summary
(1353 words, objective ~2000 words)
INTRODUCTION
Previous ICRP publications have addressed the subject of treatment of patients with radiopharmaceuticals. However, there remains knowledge gaps. Identified gaps include the need for more biokinetic and dosimetric data on the increasing practice of therapy using radiopharmaceuticals, the need for refined methods for assessing the integrity of this data, the need for extraction of useful information that will improve the understanding of patient biokinetics at therapeutic levels of radioactivity, as well as the important need to scale up the dissemination of such understanding to critical stakeholders in order to facilitate the development and use of even better therapeutic radiopharmaceuticals.
This publication addresses these gaps and provides a framework for individualized dosimetry in the planning and execution of treatment with radiopharmaceuticals, and to verify the dose to organs. The information documented in this publication, therefore, will be of immense benefit to the variety of professionals and stakeholders whose practices are crucial to the optimisation of radiopharmaceutical therapy.
RADIOPHARMACEUTICAL THERAPY METHODS: JUSTIFICATION AND OPTIMISATION
The treatment of patients using radiopharmaceuticals is a complex procedure which involves multidisciplinary input, advanced dosimetry, normal tissue detriment, and widely varying degrees of treatment outcomes. Only 131I and 32P have been used for a long time, and newer products such as 177Lu peptides and 223Ra dichloride have recently been added to the clinical practice and increasingly used. When treating individual patients, it is important to consider each product and treatment procedure together with the individual patient’s characteristics in order to optimize both the treatment and radiological protection.
This publication sets out a technical framework on which guidelines and local rules for the safe radiopharmaceutical therapy practice can be based. This framework consists of seven sub-categories which address Justification and Optimisation of protection. These sub-categories include:
The nuances, considerations that ought to be made, and the weight of current scientific evidences relevant to each treatment procedure are addressed in the above sub-categories.
BIOKINETIC DATA COLLECTION
This publication carefully enumerates the methods for biokinetic data collection, including radioactivities of whole-body, blood and tissues. In obtaining these data from organs and tissues, quantitative imaging is a common and powerful tool, whether it is planar or tomographic. Planar imaging usually using a dual-head gamma camera, is widely used for determining uptake in a source-organ of interest. Accounting for the count rates of both detectors and for body thickness, the radioactivity of a point source PQ measured by a dual-head gamma camera, APQ, can be expressed as:
APQ = (√(Ia·Ip) / C) eμe D/2
Where Ia and Ip are the anterior and posterior detector count rates respectively, μe is the effective linear attenuation coefficient, C is the calibration factor for geometric mean of both detectors, and D is the thickness of the body.
Tomographic quantitative imaging gives more accurate measurements despite some limitations. SPECT/CT imaging can be used for gamma-emitters such as 131I and 177Lu, and PET/CT imaging can be used for positron-emitters such as 124I and 86Y.
Defined protocols should be an integral part in the establishment of procedures for the biokinetic data collection. Such protocols must fundamentally include established QA/QC tasks, and carefully optimized acquisition time points.
METHODS FOR ABSORBED DOSE CALCULATIONS
The central principle in radiation therapy is to maximize radiation delivered to the cancer without exceeding the normal tissue tolerance levels. In order to determine the radiation delivered, quantitative measurements must be taken for the calculation of Absorbed Dose, D, for both the normal tissues (Dnormal) and the tumour tissue (Dtumour). The calculations for Absorbed Dose are of fundamental importance in radiological protection. These measurements can be obtained using calibrated nuclear medicine imaging systems, following carefully determined acquisition parameters.
The general equation for Absorbed Dose is well known, measured in Joules per Kilogram (J kg-1) or Gray (Gy):
D = dε / dm Gy (J kg-1)
However, accounting for the delivered radioactivity, energy of the radionuclide, biological retention, and clearance from the target organ, D can be re-expressed as:
D = (AEYØ / m) ∫0t B(t) dt Gy (J kg-1)
Where A is the activity of the radionuclide (in Bq), EY is the total energy emitted (in Joules) by the radionuclide in the organ or tissue (product of particle energy and yield), Ø is the fraction of that energy that is absorbed in the target region, m is the mass of the target region (in kg), and ∫0t B(t) dt is the biological retention of the activity integrated from time t = 0 (at injection) through complete decay or clearance (t = ∞), or until any specific time point, t (in seconds or hours).
For the purposes of radiopharmaceutical therapy, the mean Absorbed Dose is calculated by accounting for the physical half-life, the biological retention, all emission types for a given radionuclide, and the individual absorbed fractions for all radioactive emissions from that radionuclide for any source-target geometry of the human body. Factoring in these geometric variations led to the development of the Medical Internal Radiation Dose (MIRD) formation, and subsequently the MIRD/ICRP formation. According to this formation, the mean Absorbed Dose, D(rT, τ) to a target tissue rT over a defined dose integration period τ (the period τ is infinity for short-lived radiopharmaceuticals) following the administration of a radioactive material to a medical patient is given as:
D(rT, τ) = ∑rS ∫0τ A(rS, t) S(rT ← rS, t) dt Gy (J kg-1)
Where the quantity S(rT ← rS, t) is the radionuclide-specific quantity representing the mean Absorbed Dose Rate to target region rT at time t after administration per activity present in the source region rS.
Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes, in order to evaluate the reliability of the calculated Absorbed Dose. There are three main contributors to the total uncertainty in the estimation of mean Absorbed Dose, D, including:
The extent to which these uncertainties contribute, factors which affect them, and ways to minimize them have been documented.
Biological Effective Dose (BED) has been shown to be useful for describing clinically observed effects in the use of therapeutic radiopharmaceuticals.
SPECIFIC RADIOLOGICAL PROTECTION ISSUES
The practice of radiopharmaceutical therapy is a planned exposure situation. Therefore, to ensure quality practice, robust radiological protection regime must be in place. Special care must be taken to ensure that the facility for radiopharmaceutical treatment is designed and constructed to meet the requirements for optimizing radiological protection.
Justification and Optimisation of protection should be judiciously implemented to ensure not only effective treatment but also protection of patients. Although the principle of Dose Limitation is not applicable to medical exposures, a constraint of 5 mSv per episode of treatment is deemed reasonable for the relatives or members of the public who provide additional care to the patient (these exposures are also considered medical exposure). Also, in implementing Justification and Optimisation, additional care must be given to pregnant patients, breast-feeding mothers, patients on dialysis, and conception following radiopharmaceutical therapy. Local facilities should have well-established guidelines for these potential exposure scenarios, as well as safeguard against medical errors or accidents in radiopharmaceutical therapy. For instance, radiopharmaceutical therapy is contra-indicated in a pregnant patient unless it is lifesaving.
Protection of radiation workers, including medical personnel, from occupational exposure has been discussed in previous ICRP publications (75 and 103). For workers who administer therapeutic radiopharmaceuticals, protective gear and wears should be sufficiently provided. Individual and Area Monitoring must be in place. Spill and contamination control procedure should be established and supervised. Protective guidelines should be established and followed in special situations such as radiopharmaceutical therapy for an emergency or surgical patient, patient transfer to another facility after the therapy, or death of a patient following the therapy.
For occupational and public exposures, recommended Dose Limits are applied. In light of this, local guidelines must be established and followed in radiopharmaceutical therapy with respect to: release of a patient from the treatment facility, visitors coming to see the patient, a patient needing to travel, and handling of the radioactive waste associated with radiopharmaceutical therapy.
General Summary
(526 words, objective ~500 words. Readability score: 19.5, Aim for as close to 8 as possible)
The use of radiation-emitting drugs for the treatment of cancer is increasingly becoming popular in medical practice. This type of treatment is known as Radiopharmaceutical Therapy. The challenge for all radiation therapy, including radiopharmaceutical therapy, is to optimise the ability to treat cancer successfully whilst minimising potential adverse effects and normal tissue complications.When giving radiopharmaceutical therapy, the level of impact of the energy delivered to an organ or tissue is governed by the individual patient’s biological characteristics, and these characteristics may vary widely from one patient to another. Therefore, accurate measurement of how much of the delivered radiopharmaceutical is distributed in, and removed from the patient’s body gives important information on how much radiative energy was deposited in that individual patient’s organs during radiopharmaceutical therapy.
Due to differences in individual biological features, the quantity of radioactivity to be used for radiopharmaceutical therapy must be individually calculated for each patient. Theoretically, a fully personalised approach based on patient-specific quantities can ensure an appropriate radiation energy level to a tumour without exceeding normal organ and tissue toxicity thresholds.
Special consideration should be given to pregnant women. Radiopharmaceutical therapy is contraindicated in pregnancy, unless the therapy is life-saving. Female patients should be advised that breast feeding is also contraindicated after radiopharmaceutical therapy.
In addition to the patients who received radiopharmaceutical therapy, the people at risk of radiation exposure include hospital staff, members of the patient’s family (including children), carers, neighbours, and the general public. These risks can be effectively managed and mitigated with well-trained staff, appropriate facilities, appropriate dressing, established facility guidelines, as well as the use of patient-specific radiation safety precaution instructions.
Protective measures taken to minimise the exposure of medical staff to radiation include the use of proper equipment and shielding, safe handling of radioactive sources, the use of personal protective tools, continuous education and training, a commitment to awareness improvement, and the establishment of a robust safety culture. Individual monitoring of the radiation exposure to the worker must be implemented during the management of radiopharmaceutical therapy patients, and during the preparation and administration of the radiopharmaceuticals.
Medical practitioners should provide all necessary medical care consistent with patient safety and appropriate medical management. Radiological protection considerations should not prevent or delay life-saving operations in an emergency or surgical situation. Staff should be informed that a patient may be a source of radiation exposure. Appropriate training can help the staff to put risk concerns into proper perspective in these scenarios.
The decision to hospitalise or release a patient after radiopharmaceutical therapy should be made on an individual basis, considering established local guidance and regulations. Specific radiological protection precautions should be provided to patients and carers. Prevention of medical errors with radiopharmaceuticals should be an integral part in the facility design, the equipment use, and the local rules of the establishment.
Concise Summary
(137 words, objective <100 words)
The use of radiation-emitting drugs, known as radiopharmaceuticals, for the treatment of cancer is increasing. Therefore, the need to ensure successful treatment outcomes with minimal adverse effects is paramount. This publication sets out the proper framework for achieving this success by overviewing therapeutic procedures with radiopharmaceuticals, elucidating the importance of individualized approach by calculating absorbed doses to both tumours and normal tissues, and providing guidance on using this treatment method in special circumstances. It also provides information on how to protect workers, the patient’s loved ones, and the public from potential exposure after a patient is treated with radiopharmaceuticals.
ICRP, 2019. Radiological protection in therapy with radiopharmaceuticals. ICRP Publication 140. Ann. ICRP 48(1).
Authors on behalf of ICRP
Y. Yonekura, S. Mattsson, G. Flux, W.E. Bolch, L.T. Dauer, D.R. Fisher, M. Lassmann, S. Palm, M. Hosono, M. Doruff, C. Divgi, P. Zanzonico
Abstract - Radiopharmaceuticals are increasingly used for the treatment of various cancers with novel radionuclides, compounds, tracer molecules, and administration techniques. The goal of radiation therapy, including therapy with radiopharmaceuticals, is to optimise the relationship between tumour control probability and potential complications in normal organs and tissues. Essential to this optimisation is the ability to quantify the radiation doses delivered to both tumours and normal tissues. This publication provides an overview of therapeutic procedures and a framework for calculating radiation doses for various treatment approaches. In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by radiopharmaceutical uptake, retention in and clearance from the various organs and tissues of the body, together with radionuclide physical half-life. Biokinetic parameters are determined by direct measurements made using techniques that vary in complexity. For treatment planning, absorbed dose calculations are usually performed prior to therapy using a trace-labelled diagnostic administration, or retrospective dosimetry may be performed on the basis of the activity already administered following each therapeutic administration. Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes; these analyses show the reliability and quality of absorbed dose calculations. Effective dose can provide an approximate measure of lifetime risk of detriment attributable to the stochastic effects of radiation exposure, principally cancer, but effective dose does not predict future cancer incidence for an individual and does not apply to shortterm deterministic effects associated with radiopharmaceutical therapy. Accident prevention in radiation therapy should be an integral part of the design of facilities, equipment, and administration procedures. Minimisation of staff exposures includes consideration of equipment design, proper shielding and handling of sources, and personal protective equipment and tools, as well as education and training to promote awareness and engagement in radiological protection. The decision to hold or release a patient after radiopharmaceutical therapy should account for potential radiation dose to members of the public and carers that may result from residual radioactivity in the patient. In these situations, specific radiological protection guidance should be provided to patients and carers.
© 2019 ICRP. Published by SAGE.
Keywords: Radiopharmaceutical therapy; Radionuclide; Dose estimation; Radiological protection.
Key Points
Treatment with radiopharmaceuticals requires administration protocols that justify and optimise the treatment. Individual absorbed dose estimates should be performed for treatment planning and for post administration verification of doses to tumours and normal tissues.
Special consideration should be given to pregnant women and children exposed to ionising radiation. Pregnancy is usually contraindicated in radiopharmaceutical therapy. Breast feeding should be discontinued in patients receiving radiopharmaceutical therapy.
Radiation sources used in radiopharmaceutical therapy can contribute to exposures to medical personnel and others who may spend time within or adjacent to rooms that contain such sources. Meaningful radiation dose reduction and contamination control can be achieved through the use of appropriate procedures, and facility and room design, including shielding where appropriate, as well as education and training to promote awareness and engagement in radiological protection. Accident prevention and review of safe practices in radiopharmaceutical therapy should be an integral part of the design of facilities, equipment, and administration procedures.
Medical practitioners should provide all necessary medical care consistent with the radiological protection principles of justification and optimisation. Radiological protection actions should not prevent or delay life-saving medical procedures or surgery in the event that they may be required for medical care. Staff should be informed and trained with respect to patient radiation levels.
The decision to hospitalise or release a patient after therapy should be made based on existing guidance and regulations, as well as on the individual patient’s situation, considering factors such as the residual activity in the patient, the patient’s wishes, and family considerations (particularly the presence of children or pregnant family members). Information to guide radiological protection at home should be provided to patients and carers.
Executive Summary
(235) The increasing use of radiopharmaceuticals for cancer therapy promises new treatment options for patients. The challenge for all radiation therapy is to optimise the ability to treat cancer successfully (tumour control probability) against potential adverse effects and normal tissue complications. Radiopharmaceutical therapy provides opportunities to maximise the therapeutic index, a measure of both efficacy and safety.
(236) In radiopharmaceutical therapy, the absorbed dose to an organ or tissue is governed by the individual patient biokinetics (uptake, retention, and clearance), which may vary widely from one patient to another. Measurements of radiopharmaceutical biokinetics provide essential information needed for internal dose assessment.
(237) Due to biokinetic differences, personalised dosimetry must be performed for each patient. In principle, a fully personalised approach based on patient-specific measurements can ensure treatment with an appropriate activity level without exceeding normal organ and tissue toxicity thresholds.
(238) Special consideration should be given to pregnant women. Pregnancy is contraindicated in radiopharmaceutical therapy, unless the therapy is life-saving. Female patients should be advised that breast feeding is also contraindicated after therapeutic administration of radionuclides.
(239) In addition to the patients treated with radiopharmaceutical therapy, the people at risk of exposure include hospital staff, members of the patient’s family (including children), carers, neighbours, and the general public. These risks can be effectively managed and mitigated with well-trained staff, appropriate facilities, and the use of patient-specific radiation safety precaution instructions.
(240) Radiological protection measures to minimise medical staff exposures include use of proper equipment and shielding, safe handling of radioactive sources, use of personal protective equipment and tools, and education and training for commitment to improve awareness and engagement in safety practice. Individual monitoring of the worker doses and extremity doses must be considered during the management of radiopharmaceutical therapy patients, and during preparation and administration of the radiopharmaceuticals.
(241) Medical practitioners should provide all necessary medical care consistent with patient safety and appropriate medical management. Radiological protection considerations should not prevent or delay life-saving operations in the event that surgery is required. Staff should be informed when a patient may present a source of radiation exposure. Training should help the staff to put risk concerns into proper perspective.
(242) The decision to hospitalise or release a patient after therapy should be made on an individual basis, considering factors such as the residual activity in the patient and existing guidance and regulations. Specific radiological protection precautions should be provided to patients and carers.
(243) Prevention of medical errors with radiopharmaceuticals should be an integral part of the design of equipment and premises, and of the working procedures.
Technical summary
(1353 words, objective ~2000 words)
INTRODUCTION
Previous ICRP publications have addressed the subject of treatment of patients with radiopharmaceuticals. However, there remains knowledge gaps. Identified gaps include the need for more biokinetic and dosimetric data on the increasing practice of therapy using radiopharmaceuticals, the need for refined methods for assessing the integrity of this data, the need for extraction of useful information that will improve the understanding of patient biokinetics at therapeutic levels of radioactivity, as well as the important need to scale up the dissemination of such understanding to critical stakeholders in order to facilitate the development and use of even better therapeutic radiopharmaceuticals.
This publication addresses these gaps and provides a framework for individualized dosimetry in the planning and execution of treatment with radiopharmaceuticals, and to verify the dose to organs. The information documented in this publication, therefore, will be of immense benefit to the variety of professionals and stakeholders whose practices are crucial to the optimisation of radiopharmaceutical therapy.
RADIOPHARMACEUTICAL THERAPY METHODS: JUSTIFICATION AND OPTIMISATION
The treatment of patients using radiopharmaceuticals is a complex procedure which involves multidisciplinary input, advanced dosimetry, normal tissue detriment, and widely varying degrees of treatment outcomes. Only 131I and 32P have been used for a long time, and newer products such as 177Lu peptides and 223Ra dichloride have recently been added to the clinical practice and increasingly used. When treating individual patients, it is important to consider each product and treatment procedure together with the individual patient’s characteristics in order to optimize both the treatment and radiological protection.
This publication sets out a technical framework on which guidelines and local rules for the safe radiopharmaceutical therapy practice can be based. This framework consists of seven sub-categories which address Justification and Optimisation of protection. These sub-categories include:
- Aim of the treatment.
- Treatment protocols.
- Radiation dose to friends and family.
- Radiation dose to staff.
- Patient organ dosimetry.
- Risks to the patient.
- Recommendations.
The nuances, considerations that ought to be made, and the weight of current scientific evidences relevant to each treatment procedure are addressed in the above sub-categories.
BIOKINETIC DATA COLLECTION
This publication carefully enumerates the methods for biokinetic data collection, including radioactivities of whole-body, blood and tissues. In obtaining these data from organs and tissues, quantitative imaging is a common and powerful tool, whether it is planar or tomographic. Planar imaging usually using a dual-head gamma camera, is widely used for determining uptake in a source-organ of interest. Accounting for the count rates of both detectors and for body thickness, the radioactivity of a point source PQ measured by a dual-head gamma camera, APQ, can be expressed as:
APQ = (√(Ia·Ip) / C) eμe D/2
Where Ia and Ip are the anterior and posterior detector count rates respectively, μe is the effective linear attenuation coefficient, C is the calibration factor for geometric mean of both detectors, and D is the thickness of the body.
Tomographic quantitative imaging gives more accurate measurements despite some limitations. SPECT/CT imaging can be used for gamma-emitters such as 131I and 177Lu, and PET/CT imaging can be used for positron-emitters such as 124I and 86Y.
Defined protocols should be an integral part in the establishment of procedures for the biokinetic data collection. Such protocols must fundamentally include established QA/QC tasks, and carefully optimized acquisition time points.
METHODS FOR ABSORBED DOSE CALCULATIONS
The central principle in radiation therapy is to maximize radiation delivered to the cancer without exceeding the normal tissue tolerance levels. In order to determine the radiation delivered, quantitative measurements must be taken for the calculation of Absorbed Dose, D, for both the normal tissues (Dnormal) and the tumour tissue (Dtumour). The calculations for Absorbed Dose are of fundamental importance in radiological protection. These measurements can be obtained using calibrated nuclear medicine imaging systems, following carefully determined acquisition parameters.
The general equation for Absorbed Dose is well known, measured in Joules per Kilogram (J kg-1) or Gray (Gy):
D = dε / dm Gy (J kg-1)
However, accounting for the delivered radioactivity, energy of the radionuclide, biological retention, and clearance from the target organ, D can be re-expressed as:
D = (AEYØ / m) ∫0t B(t) dt Gy (J kg-1)
Where A is the activity of the radionuclide (in Bq), EY is the total energy emitted (in Joules) by the radionuclide in the organ or tissue (product of particle energy and yield), Ø is the fraction of that energy that is absorbed in the target region, m is the mass of the target region (in kg), and ∫0t B(t) dt is the biological retention of the activity integrated from time t = 0 (at injection) through complete decay or clearance (t = ∞), or until any specific time point, t (in seconds or hours).
For the purposes of radiopharmaceutical therapy, the mean Absorbed Dose is calculated by accounting for the physical half-life, the biological retention, all emission types for a given radionuclide, and the individual absorbed fractions for all radioactive emissions from that radionuclide for any source-target geometry of the human body. Factoring in these geometric variations led to the development of the Medical Internal Radiation Dose (MIRD) formation, and subsequently the MIRD/ICRP formation. According to this formation, the mean Absorbed Dose, D(rT, τ) to a target tissue rT over a defined dose integration period τ (the period τ is infinity for short-lived radiopharmaceuticals) following the administration of a radioactive material to a medical patient is given as:
D(rT, τ) = ∑rS ∫0τ A(rS, t) S(rT ← rS, t) dt Gy (J kg-1)
Where the quantity S(rT ← rS, t) is the radionuclide-specific quantity representing the mean Absorbed Dose Rate to target region rT at time t after administration per activity present in the source region rS.
Uncertainty analyses provide additional information about sources of bias and random variation and their magnitudes, in order to evaluate the reliability of the calculated Absorbed Dose. There are three main contributors to the total uncertainty in the estimation of mean Absorbed Dose, D, including:
- Measurement uncertainties.
- Uncertainties associated with estimating the integrated activity in organs.
- The use of models/phantoms.
The extent to which these uncertainties contribute, factors which affect them, and ways to minimize them have been documented.
Biological Effective Dose (BED) has been shown to be useful for describing clinically observed effects in the use of therapeutic radiopharmaceuticals.
SPECIFIC RADIOLOGICAL PROTECTION ISSUES
The practice of radiopharmaceutical therapy is a planned exposure situation. Therefore, to ensure quality practice, robust radiological protection regime must be in place. Special care must be taken to ensure that the facility for radiopharmaceutical treatment is designed and constructed to meet the requirements for optimizing radiological protection.
Justification and Optimisation of protection should be judiciously implemented to ensure not only effective treatment but also protection of patients. Although the principle of Dose Limitation is not applicable to medical exposures, a constraint of 5 mSv per episode of treatment is deemed reasonable for the relatives or members of the public who provide additional care to the patient (these exposures are also considered medical exposure). Also, in implementing Justification and Optimisation, additional care must be given to pregnant patients, breast-feeding mothers, patients on dialysis, and conception following radiopharmaceutical therapy. Local facilities should have well-established guidelines for these potential exposure scenarios, as well as safeguard against medical errors or accidents in radiopharmaceutical therapy. For instance, radiopharmaceutical therapy is contra-indicated in a pregnant patient unless it is lifesaving.
Protection of radiation workers, including medical personnel, from occupational exposure has been discussed in previous ICRP publications (75 and 103). For workers who administer therapeutic radiopharmaceuticals, protective gear and wears should be sufficiently provided. Individual and Area Monitoring must be in place. Spill and contamination control procedure should be established and supervised. Protective guidelines should be established and followed in special situations such as radiopharmaceutical therapy for an emergency or surgical patient, patient transfer to another facility after the therapy, or death of a patient following the therapy.
For occupational and public exposures, recommended Dose Limits are applied. In light of this, local guidelines must be established and followed in radiopharmaceutical therapy with respect to: release of a patient from the treatment facility, visitors coming to see the patient, a patient needing to travel, and handling of the radioactive waste associated with radiopharmaceutical therapy.
General Summary
(526 words, objective ~500 words. Readability score: 19.5, Aim for as close to 8 as possible)
The use of radiation-emitting drugs for the treatment of cancer is increasingly becoming popular in medical practice. This type of treatment is known as Radiopharmaceutical Therapy. The challenge for all radiation therapy, including radiopharmaceutical therapy, is to optimise the ability to treat cancer successfully whilst minimising potential adverse effects and normal tissue complications.When giving radiopharmaceutical therapy, the level of impact of the energy delivered to an organ or tissue is governed by the individual patient’s biological characteristics, and these characteristics may vary widely from one patient to another. Therefore, accurate measurement of how much of the delivered radiopharmaceutical is distributed in, and removed from the patient’s body gives important information on how much radiative energy was deposited in that individual patient’s organs during radiopharmaceutical therapy.
Due to differences in individual biological features, the quantity of radioactivity to be used for radiopharmaceutical therapy must be individually calculated for each patient. Theoretically, a fully personalised approach based on patient-specific quantities can ensure an appropriate radiation energy level to a tumour without exceeding normal organ and tissue toxicity thresholds.
Special consideration should be given to pregnant women. Radiopharmaceutical therapy is contraindicated in pregnancy, unless the therapy is life-saving. Female patients should be advised that breast feeding is also contraindicated after radiopharmaceutical therapy.
In addition to the patients who received radiopharmaceutical therapy, the people at risk of radiation exposure include hospital staff, members of the patient’s family (including children), carers, neighbours, and the general public. These risks can be effectively managed and mitigated with well-trained staff, appropriate facilities, appropriate dressing, established facility guidelines, as well as the use of patient-specific radiation safety precaution instructions.
Protective measures taken to minimise the exposure of medical staff to radiation include the use of proper equipment and shielding, safe handling of radioactive sources, the use of personal protective tools, continuous education and training, a commitment to awareness improvement, and the establishment of a robust safety culture. Individual monitoring of the radiation exposure to the worker must be implemented during the management of radiopharmaceutical therapy patients, and during the preparation and administration of the radiopharmaceuticals.
Medical practitioners should provide all necessary medical care consistent with patient safety and appropriate medical management. Radiological protection considerations should not prevent or delay life-saving operations in an emergency or surgical situation. Staff should be informed that a patient may be a source of radiation exposure. Appropriate training can help the staff to put risk concerns into proper perspective in these scenarios.
The decision to hospitalise or release a patient after radiopharmaceutical therapy should be made on an individual basis, considering established local guidance and regulations. Specific radiological protection precautions should be provided to patients and carers. Prevention of medical errors with radiopharmaceuticals should be an integral part in the facility design, the equipment use, and the local rules of the establishment.
Concise Summary
(137 words, objective <100 words)
The use of radiation-emitting drugs, known as radiopharmaceuticals, for the treatment of cancer is increasing. Therefore, the need to ensure successful treatment outcomes with minimal adverse effects is paramount. This publication sets out the proper framework for achieving this success by overviewing therapeutic procedures with radiopharmaceuticals, elucidating the importance of individualized approach by calculating absorbed doses to both tumours and normal tissues, and providing guidance on using this treatment method in special circumstances. It also provides information on how to protect workers, the patient’s loved ones, and the public from potential exposure after a patient is treated with radiopharmaceuticals.
