Radiopharmaceuticals for nuclear cardiology: radiation dosimetry, uncertainties, and risk

The technical basis for the dose estimates for several radiopharmaceuticals used in nuclear cardiology is reviewed, and cases in which uncertainty has been encountered in the dosimetry of an agent are discussed. Also discussed is the issue of uncertainties in radiation dose estimates and how to compare the relative risks of studies. METHODS: Radiation dose estimates (organ absorbed doses and effective doses) from different literature sources were directly compared. Typical values for administered activity per study were used to compare doses that are to be expected in clinical applications. RESULTS: The effective doses for all agents varied from 2 to 15 mSv per study, with the lowest values being seen for (13)N-NH(3) and (15)O-H(2)O studies and the highest values being seen for (201)Tl-chloride studies. The effective doses for (99m)Tc- and (201)Tl-labeled agents differed by about a factor of 2, a factor that is comparable to the uncertainty in individual values. This uncertainty results from the application of standard anthropomorphic and biokinetic models, presumably representative of the exposed population, to individual patients. CONCLUSION: Considerations such as diagnostic accuracy, ease of use, image quality, and patient comfort and convenience should generally dictate the choice of a radiopharmaceutical, with radiation dose being only a secondary or even tertiary consideration. Counseling of nuclear medicine patients who may be concerned about exposure should include a reasonable estimate of the median dose for the type of examination and administered activity of the radiopharmaceutical; in addition, it should be explained that the theoretic risks of the procedure are orders of magnitude lower than the actual benefits of the examination. Providing numeric estimates of risks from studies to individual patients is inappropriate, given the uncertainties in the dose estimates and the limited predictive power of current dose-risk models in the low-dose (i.e., diagnostic) range.     

The new EANM paediatric dosage card

Introduction In a recent publication, Jacobs et al. proposed the use of three tracer-dependent dosage cards for paediatric nuclear medicine. Materials and methods Based upon this work, the EANM dosimetry and paediatrics committees introduce a condensed and revised version of this dosage card for major nuclear medicine paediatric diagnostic procedures, replacing the previous card by Piepsz et al. and including a set of minimum activities. Results The activities to be administered result in weight-independent effective doses to the children. In addition, the introduction of minimum activities guarantees a minimum standard of image quality throughout Europe and avoids a variety of administered activities in children of the same weight in different countries, which was the case when using the previous EANM dosage card. for the EANM Dosimetry (M Lassmann, M. Monsieurs) and Paediatrics (L. Biassoni, C. Franzius) Committees     

Practical determination of patient-specific marrow dose using radioactivity concentration in blood and body.

Accurate determination of red marrow radiation is important because myelotoxicity is often dose limiting in radioimmunotherapy. The S-value methodology assumes a fixed red marrow mass as defined by the standard Medical Internal Radiation Dose (MIRD) mathematic phantom. Substantial error can be introduced in marrow radiation estimates because red marrow mass varies from patient to patient. In this work we describe a patient-specific marrow dosimetry methodology that does not require an explicit estimate of marrow mass. METHODS: Photon radiation to marrow from all sources can be considered as the total body to marrow. Based on photon radiation from body and electron radiation from blood, a patient-specific marrow dose can be determined by counting blood and total body radioactivity and measuring body weight. RESULTS: The deviation in marrow dose calculation using total body to represent all photon radiation was 3.9% in 66 patients administered 131I-labeled antibodies and was 9.1% in 18 patients administered 67Cu-labeled antibodies. The differences between this patient-specific approach and estimates based on standard anatomy were considerable, ranging from -35% to 88%. The differences were greater when patients' weights differed substantially from the MIRD reference man phantom. CONCLUSION: For radiopharmaceuticals that do not bind marrow, patient-specific marrow dosimetry can be independent of the actual marrow mass of a patient. Patient-specific marrow dosimetry can be determined using radioactivity concentration in blood and body.     

Internal radionuclide radiation dosimetry: a review of basic concepts and recent developments.

Internal dosimetry deals with the determination of the amount and the spatial and temporal distribution of radiation energy deposited in tissue by radionuclides within the body. Nuclear medicine has been largely a diagnostic specialty, and model-derived average organ dose estimates for risk assessment, the traditional application of the MIRD schema, have proven entirely adequate. However, to the extent that specific patients deviate kinetically and anatomically from the model used, such dose estimates will be inaccurate. With the increasing therapeutic application of internal radionuclides and the need for greater accuracy, radiation dosimetry in nuclear medicine is evolving from population- and organ-average to patient- and position-specific dose estimation. Beginning with the relevant quantities and units, this article reviews the historical methods and newly developed concepts and techniques to characterize radionuclide radiation doses. The latter include the 3 principal approaches to the calculation of macroscopic nonuniform dose distributions: dose point-kernel convolution, Monte Carlo simulation, and voxel S factors. Radiation dosimetry in "sensitive" populations, including pregnant women, nursing mothers, and children, also will be reviewed.     

Radiation dosimetry in nuclear medicine.

Radionuclides are used in nuclear medicine in a variety of diagnostic and therapeutic procedures. A knowledge of the radiation dose received by different organs in the body is essential to an evaluation of the risks and benefits of any procedure. In this paper, current methods for internal dosimetry are reviewed, as they are applied in nuclear medicine. Particularly, the Medical Internal Radiation Dose (MIRD) system for dosimetry is explained, and many of its published resources discussed. Available models representing individuals of different age and gender, including those representing the pregnant woman are described; current trends in establishing models for individual patients are also evaluated. The proper design of kinetic studies for establishing radiation doses for radiopharmaceuticals is discussed. An overview of how to use information obtained in a dosimetry study, including that of the effective dose equivalent (ICRP 30) and effective dose (ICRP 60), is given. Current trends and issues in internal dosimetry, including the calculation of patient-specific doses and in the use of small scale and microdosimetry techniques, are also reviewed.     

Minimizing and communicating radiation risk in pediatric nuclear medicine

The value of pediatric nuclear medicine is well established. Pediatric patients are referred to nuclear medicine from nearly all pediatric specialties including urology, oncology, cardiology, gastroenterology, and orthopedics. Radiation exposure is associated with a potential, small, risk of inducing cancer in the patient later in life and is higher in younger patients. Recently, there has been enhanced interest in exposure to radiation from medical imaging. Thus, it is incumbent on practitioners of pediatric nuclear medicine to have an understanding of dosimetry and radiation risk to communicate effectively with their patients and their families. This article reviews radiation dosimetry for radiopharmaceuticals and also CT given the recent proliferation of PET/CT and SPECT/CT. It also describes the scientific basis for radiation risk estimation in the context of pediatric nuclear medicine. Approaches for effective communication of risk to patients' families are discussed. Lastly, radiation dose reduction in pediatric nuclear medicine is explicated.     

Myeloablative 131I-tositumomab radioimmunotherapy in treating non-Hodgkin's lymphoma: comparison of dosimetry based on whole-body retention and dose to critical organ receiving the highest dose.

Myeloablative radioimmunotherapy using (131)I-tositumomab (anti-CD20) monoclonal antibodies is an effective therapy for B-cell non-Hodgkin's lymphoma. The amount of radioactivity for radioimmunotherapy may be determined by several methods, including those based on whole-body retention and on dose to a limiting normal organ. The goal of each approach is to deliver maximal myeloablative amounts of radioactivity within the tolerance of critical normal organs. METHODS: Records of 100 consecutive patients who underwent biodistribution and dosimetry evaluation after tracer infusion of (131)I-tositumomab before radioimmunotherapy were reviewed. We assessed organ and tissue activities over time by serial gamma-camera imaging to calculate radiation-absorbed doses. Organ volumes were determined from CT scans for organ-specific dosimetry. These dose estimates helped us to determine therapy on the basis of projected dose to the critical normal organ receiving a maximum tolerable radiation dose. We compared organ-specific dosimetry for treatment planning with the whole-body dose-assessment method by retrospectively analyzing the differences in projected organ-absorbed doses and their ratios. RESULTS: Mean organ doses per unit of administered activity (mGy/MBq) estimated by both methods were 0.33 for liver and 0.33 for lungs by the whole-body method and 1.52 for liver and 1.74 for lungs by the organ-specific method (P=0.0001). The median differences between methods were 0.92 mGy/MBq (range, 0.36-2.2 mGy/MBq) for lungs, 0.82 mGy/MBq (range, 0.28-1.67 mGy/MBq) for liver, and -0.01 mGy/MBq (range, -0.18-0.16 mGy/MBq) for whole body. The median ratios of the treatment activities based on limiting normal-organ dose were 5.12 (range, 2.33-10.01) for lungs, 4.14 (range, 2.16-6.67) for liver, and 0.94 (range, 0.79-1.22) for whole body. We found substantial differences between the dose estimated by the 2 methods for liver and lungs (P=0.0001). CONCLUSION: Dosimetry based on whole-body retention will underestimate the organ doses, and a preferable approach is to evaluate organ-specific doses by accounting for actual radionuclide biodistribution. Myeloablative treatments based on the latter approach allow administration of the maximum amount of radioactivity while minimizing toxicity.     

Canadian Cytogenetic Emergency network (CEN) for biological dosimetry following radiological/nuclear accidents

PURPOSE: To test the ability of the cytogenetic emergency network (CEN) of laboratories, currently under development across Canada, to provide rapid biological dosimetry using the dicentric assay for triage assessment, that could be implemented in the event of a large-scale radiation/nuclear emergency. MATERIALS AND METHODS: A workshop was held in May 2004 in Toronto, Canada, to introduce the concept of CEN and recruit clinical cytogenetic laboratories at hospitals across the country. Slides were prepared for dicentric assay analysis following in vitro irradiation of blood to a range of gamma-ray doses. A minimum of 50 metaphases per slide were analyzed by 41 people at 22 different laboratories to estimate the exposure level. RESULTS: Dose estimates were calculated based on a dose response curve generated at Health Canada. There were a total of 104 dose estimates and 96 (92.3%) of them fell within the expected range using triage scoring criteria. Half of the laboratories analyzed 50 metaphases in 相似文献   

Techniques for using Bexxar for the treatment of non-Hodgkin's lymphoma

OBJECTIVE: This article briefly describes the concept of radioimmunotherapy and treatment of non-Hodgkin's lymphoma by a new radiopharmaceutical that uses this technique. The rationale for such an approach is reviewed, and some of the practical consequences for technologists are examined. These include the idea of performing individually customized dosimetry and using relatively high (131)I doses on an outpatient basis. After reading this article, the nuclear medicine technologist should be able to (a) describe radioimmunotherapy and its advantages, (b) explain why treatment of non-Hodgkin's lymphoma is enhanced by this technique, (c) understand the role of the predose study and its use in determining the therapeutic dose, and (d) recognize the radiation safety issues involved with the therapeutic dose administration and patient release criteria.     

Diagnostic reference value. Critical evaluation of the term with the example of nuclear medicine studies in Austria

The aim of this study was to collect administered activities of important nuclear medicine diagnostic examinations and to identify frequencies as well as age distributions in the light of hybrid devices in Austria. Based on the survey data a re-evaluation of dose reference levels for nuclear medicine has been published in June 2010 in the novella of the Austrian Medical Radiation Protection Regulation (MedStrSchV) (8), also an estimate of the average individual doses of the total population. Accurate data on nuclear medicine studies of 34% of all Austrian nuclear medicine units could be collected. RESULTS: Extrapolated there are about 150000 nuclear medicine examinations per year performed in Austria. The median age of patients is thereby 62 years. The results of this study resulted in 65% of the dose reference values to change, whereas 48% had to be revised downwards and 17% upwards. Additionally, 5 new reference values were included in the list; three more were taken out, however. The estimation of the individual effective patient dose for each offered examination was on average 4.7 mSv. An extrapolation based on the total exposure of the population with regard to uninvolved persons and children led to 0.07 mSv per year by nuclear medicine examinations. CONCLUSION: The published diagnostic reference values correspond to the normal investigative practice in Austria and are compliant with most international recommendations. The term "optimal value" has been removed from the text of the law, because such wording would be misleading.     

Radiation dose to the hands in nuclear medicine

Study of the distribution of radiation dose across both hands during the dispensing and administration of radiopharmaceuticals is useful in the assessment of the extremity doses received by nuclear medicine personnel. Some staff in the UK have already been designated as classified radiation workers due to the radiation doses that their hands may receive. With possible forthcoming reductions in the dose limits, it is important that as much data as possible is available on such dosimetry. By measuring the dose at nine different locations on each hand, an optimal site (the base of the second digit) to represent a more accurate 'mean hand dose' could be determined. The use of inserting different butterfly cannula into a vein, prior to radiopharmaceutical administration, was assessed in terms of the dose reduction effect to the member of staff performing the task. It was found that a long tubing cannula (300 mm) did not significantly reduce the radiation dose of the operator whereas shorter ones (95 mm) gave a very significant dose reduction.     

Canadian Cytogenetic Emergency Network (CEN) for biological dosimetry following radiological/nuclear accidents

Purpose: To test the ability of the cytogenetic emergency network (CEN) of laboratories, currently under development across Canada, to provide rapid biological dosimetry using the dicentric assay for triage assessment, that could be implemented in the event of a large-scale radiation/nuclear emergency.

Materials and methods: A workshop was held in May 2004 in Toronto, Canada, to introduce the concept of CEN and recruit clinical cytogenetic laboratories at hospitals across the country. Slides were prepared for dicentric assay analysis following in vitro irradiation of blood to a range of gamma-ray doses. A minimum of 50 metaphases per slide were analyzed by 41 people at 22 different laboratories to estimate the exposure level.

Results: Dose estimates were calculated based on a dose response curve generated at Health Canada. There were a total of 104 dose estimates and 96 (92.3%) of them fell within the expected range using triage scoring criteria. Half of the laboratories analyzed 50 metaphases in ≤ 1 hour and the time to score them was proportional to dose. The capacity and scoring expertise of the various participating laboratories were found to be generally acceptable.

Conclusions: The dose estimates generated through triage scoring by this network were acceptable for emergency biological dosimetry. When this network is fully operational, it will be the first of its kind in Canada able to respond to radiological/nuclear emergencies by providing triage quality biological dosimetry for a large number of samples. This network represents an alternate expansion of existing international emergency biological dosimetry cytogenetic networks.     

Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison.

Standardization of marrow dosimetry is of considerable importance when estimating dose-response for a multicentered clinical trial involving radionuclide therapy. However, it is only within the past five years that the intercomparison of marrow dosimetry results among separate clinical trials that use the same agent has become scientifically feasible. In this work, we have analyzed reported marrow dosimetry results from radioimmunotherapy trials and recalculated marrow absorbed doses at a central facility using a standard blood model with patient-specific source data. The basic approach used in the American Association of Physicists in Medicine (AAPM)/Sgouros marrow dosimetry methodology was common to calculation performed at all participating institutions, including the central facility. Differences in dose estimates associated with starting assumptions and the exact implementation of the AAPM/Sgouros calculation methodology used by the source institutions and the central facility were quantified and compared. METHODS: Data from 22 patients enrolled in radiolabeled antibody clinical trials were randomly selected from 7 participating institutions for the assessment of marrow dose. The analysis was restricted to those patients who were treated with 131I- or 186Re-labeled antibody and had no marrow involvement. Calculation of bone marrow dose at each participating institution was unique to the trial or institution, but all used some form of the AAPM/Sgouros blood model approach. The central facility adopted a marrow dosimetry model based on the AAPM/Sgouros model for radiolabeled antibodies using the standard MIRD approach to the remainder-of-body contribution. A standardized approach to account for variations in patient mass was used for the remainder-of-body component. To simplify clinical implementation, regional marrow uptake and time-dependent changes in the marrow-to-blood concentration ratio were not included. Methods of formatting the collection of standard datasets useful in defining dose-response parameters are also presented. RESULTS: Bone marrow doses were calculated according to the method described for each of the 22 patients based on the patient-specific data supplied by the participating institutions. These values were then individually compared with the marrow doses originally reported by each institution. Comparison of the two calculation methods was expressed as a ratio of the marrow doses for each patient. The mean ratio for the dose estimates at the participating institution calculation compared with the central laboratory value was 0.920 +/- 0.259 (mean +/- SD), with a range from 0.708 to 1.202. CONCLUSION: The independent use of the AAPM/Sgouros method blood model approach to marrow dosimetry has brought these dose estimates to within 30% of the results obtained centrally compared with substantially higher uncertainties reported previously. Variations in calculation methodology or initial assumptions adopted by individual institutions may still contribute significant uncertainty to dose estimates, even when the same data are used as a starting point for the calculation comparison shown here. A clinically relevant, standard method for marrow dosimetry for radiolabeled antibodies is proposed as a benchmark for intercomparison purposes. A parameter sensitivity analysis and a summary discussion of the use of this model for potentially improving dose-response data correlation are also presented.     

Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck.

This study assessed the radiation dosimetry of 99mTc-labeled ethylene dicysteine (EC) C225 (EC-C225), a promising radioligand for functional tumor imaging. METHODS: Whole-body scanning was performed on 6 patients with head and neck squamous cell carcinoma up to 24 h after administration of 99mTc-EC-C225. Alternate patients who had been randomized to receive C225 in a phase III trial received 99mTc-EC-C225 before their 20-mg test dose or after their 400 mg/m2 loading dose of unlabeled C225 (patients 1/3/5 and 2/4/6, respectively). Radiation dosimetry was assessed using the MIRD method. RESULTS: The critical organ was the kidney, with an average radiation-absorbed dose for all 6 patients of 0.0274 mGy/MBq. The average total-body absorbed dose was 0.0022 mGy/MBq (0.243 cGy/1,110 MBq). CONCLUSION: The new radiopharmaceutical 99mTc-EC-C225 appears to have reasonable dosimetric properties for a diagnostic nuclear medicine agent. Correlation of the imaging results with clinical findings is the next step.     

Patient-specific, 3-dimensional dosimetry in non-Hodgkin's lymphoma patients treated with 131I-anti-B1 antibody: assessment of tumor dose-response.

A comprehensive, SPECT-based, patient-specific 3-dimensional (3D) dosimetry analysis has been performed using 3D-ID, a previously developed software package. The role of the total-body tumor burden, individual lesion size, tumor absorbed dose, and the spatial distribution of the absorbed dose on response and on the time course of tumor shrinkage has been examined in patients with lymphoma treated by radioimmunotherapy. METHODS: Data from 15 patients participating in a phase II study of (131)I-labeled anti-B1 antibody (tositumomab) were used. Patients were administered a tracer dose of (131)I for imaging and pharmacokinetics. Dose estimates from the tracer studies were used to prescribe the therapeutic administration such that the whole-body absorbed dose did not exceed 75 cGy. All patients received a fixed mass amount of antibody for both the tracer and the therapeutic administrations. SPECT and planar imaging were performed 3-4 d after the therapeutic administration. CT or MRI scans were available on all patients. Total tumor burden was assessed by drawing contours around all lymphoma lesions identified on whole-body CT or MRI. Mean absorbed doses were estimated for selected, index lesions by conventional dosimetry and also by 3D SPECT-based dosimetry. Using a patient-specific dosimetry package, 3D-ID, dose-volume histograms were also generated to assess the spatial distribution of absorbed dose. This approach made it possible to obtain estimates of the minimum and maximum absorbed doses for individual tumors in addition to the mean. RESULTS: Mean absorbed dose estimates obtained by patient-specific SPECT-based dosimetry using 3D-ID were within 2%-5% of estimates obtained by conventional dosimetry. None of the absorbed dose parameters (mean, minimum, maximum, uniformity) were found to have a significant correlation with tumor response. The total-body tumor burden did not impact on overall response or toxicity. CONCLUSION: This analysis represents the first full reported implementation of a patient-specific 3D dosimetry package. The absence of a dose-response relationship for tumors is surprising and suggests that absorbed dose is not the sole determinant of tumor response in these patients. The absence of a correlation between the total-body tumor burden and overall response or toxicity suggests that tailoring the milligram amount of administered antibody to patient tumor burden is not likely to improve response or reduce toxicity.     

Pattern of radiopharmaceutical administration to patients between 1982 and 1986

Analysis of the workload of a nuclear medicine department over the period 1982 to 1986 has shown the prevalence of repeated investigations in individual patients. Records from 23,152 investigations on 17,063 patients indicated that 88.5% received a single administration and only 0.5% received more than four doses of the same radiopharmaceutical. Patterns of usage of a wide range of radiopharmaceuticals are presented and show that the technetium bone imaging agent is the radiopharmaceutical most commonly used for repeated administrations. Analysis of the radiation dose to individual patients arising from radiopharmaceutical administration has shown that only two patients in the survey exceeded 50 mSv per annum and approximately 25% of patients exceeded 5 mSv per annum.     

A radiopharmaceuticals schedule for imaging in paediatrics

There is no standard schedule for the amounts of radiopharmaceutical administered to children at present. Various alternative methods are currently in practice, all with some support from the literature. Optimization of the amount of radiopharmaceutical to be administered is discussed in relation to the radiation burden of such an examination. The Paediatric Task Group of the European Association of Nuclear Medicine has investigated the current situation and now suggests a method for standardization of administered amounts of radiopharmaceutical in paediatrics. The fraction of the adult amount of radiopharmaceutical to be administered should be calculated from the child's body weight according to the accompanying table. In small infants, the minimum amount of a radiopharmaceutical is discussed and suggested amounts to be administered are presented.     

Nuclear medicine practice in Japan: A report of the 5th nationwide survey in 2002

The Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every five years since 1982 to provide detailed information on its current status. METHODS: Questionnaires were sent to every institution known to the Japan Radioisotope Association to provide nuclear medicine examinations. The questionnaires address the number and kind of nuclear medicine examinations performed as well as the kind and dose of the radiopharmaceuticals used during the month of June 2002. The annual number of total or specific examinations was then estimated. RESULTS: Of the institutions sent questionnaires, 1,204 were for in vivo study, 124 were for in vitro study, and 36 were for positron emission tomography (PET) study. Out of these, 95.8% answered them. A total of 1,697 gamma cameras were installed in 1,160 facilities, of which 50% were dual-head cameras. The estimated total annual number of examinations expressed by the number of administered radiopharmaceuticals was 1.60 million, similar to that of the previous survey (1997). The frequency of study with single photon emission computed tomography (SPECT) increased to 40%, from 30% in the previous survey. The scintigraphy most frequently performed was bone (35%), followed by myocardium (24%) and brain perfusion (12%). All showed a continuous increase over the past 20 years. Tumor imaging, however, fell from third to fourth place. The most commonly used radiopharmaceutical for each scintigraphy was 99mTc-HMDP for bone, 201Tl-chloride for myocardium, 67Ga-citrate for tumor, and 123I-IMP for brain. A total of 29,376 PET studies were performed yearly. Among them, 18F-FDG rapidly increased 3.7-fold. 131I therapy for thyroid cancer and hyperthyroidism was conducted yearly in 1,647 and 3,347 patients, respectively. A total of 31.35 million in vitro radioassays were carried out yearly, the number of which has been decreasing continuously since 1992. CONCLUSIONS: It was proved that the content of nuclear medicine practice in Japan has changed in the past five years. This report might be useful for understanding the current trends of nuclear medicine practice in Japan.     

A radiopharmaceuticals schedule for imaging in paediatrics. Paediatric Task Group European Association Nuclear Medicine

There is no standard schedule for the amounts of radiopharmaceutical administered to children at present. Various alternative methods are currently in practice, all with some support from the literature. Optimization of the amount of radiopharmaceutical to be administered is discussed in relation to the radiation burden of such an examination. The Paediatric Task Group of the European Association of Nuclear Medicine has investigated the current situation and now suggests a method for standardization of administered amounts of radiopharmaceutical in paediatrics. The fraction of the adult amount of radiopharmaceutical to be administered should be calculated from the child's body weight according to the accompanying table. In small infants, the minimum amount of a radiopharmaceutical is discussed and suggested amounts to be administered are presented.     

Dosimetry in radionuclide therapies with 90Y-conjugates: the IEO experience.

The basis for a successful radionuclide therapy is a high and stable uptake of the radiopharmaceutical in the target tissue along with low activity concentration in other normal organs. The contribution of dosimetry in radionuclide therapy is to predict before the treatment the absorbed doses in tumor and normal organs, to identify the critical organs, to minimize any possible toxicity and to evaluate the maximum tolerated dose. We report our experience concerning pharmacokinetics and dosimetry of two 90Y-therapeutic protocols: 3-step pretargeting radioimmunotherapy (RIT) according to the biotin-avidin system and receptor mediated radionuclide therapy with the somatostatin analogue [DOTA-D-Phe1-Tyr3] octreotide named DOTATOC. For the dosimetric analysis, analogous approaches for the two radiolabeled compounds due to the similar pharmacokinetic characteristics were adopted; the MIRD formalism was applied, taking into account both the physical and the biological characteristics of the radioconjugate and patients' metabolism. In order to determine biological clearance, serial blood samples and complete urine collection were obtained up to 48 hours after injection; to evaluate biodistribution, several whole body scans were acquired. Both therapies showed the advantageous characteristics of a fast blood clearance and a predominantly renal excretion of the radiopharmaceuticals thus lowering the irradiation of the total body. Although pharmacokinetic characteristis were similar, different critical organs were found for the two therapies; in particular, some considerations regarding red marrow, spleen and kidneys were required. The results of our studies indicate that high activities of 90Y-biotin (3-step RIT) and 90Y-DOTATOC can be administered with acceptable radiation doses to normal organs.