Radioiodine-131 therapy (RIT) in benign thyroid diseases: Personalized prescription based on objectives with optional use of pharmacological modulators

¹³¹I therapy (RIT) in benign thyroid diseases is the oldest and most currently used application of internal radiotherapy. With the new molecular ¹²³I-TS images one may identify 15 presentations that can benefit from RIT. With three groups of activity determination corresponding to a dozen approaching protocols, several judgmental criteria (eu-, hypo-, hyperthyroidism, relapses etc.) and varying timeframes to assess the success, a “best method of activity calculation” makes little sense. Four clinical objectives must be first identified (goal): antitoxic (euthyroidism), ablative (hypothyroidism), reductive (to reduce a targeted volume) and preventive (to prevent progression from compensated to overt hyperthyroidism) ¹³¹I-RIT. A dose response relationship as regards the target volume reduction is firmly established in the short term (1-year) and explains the clinical outcome in Thyroid Functional Autonomy (TFA). In Grave's disease (GD), other factors may interfere that make the long-term function less predictable. Pharmacological modulators of ¹³¹I-RIT such as antithyroid drugs (ATDs) and LT3 must be skillfully handled. ATDs interfere with iodine kinetics, enhance the heterogeneity of the spatial dose deposition and diminish the accuracy of absorbed dose deposition, especially when using poorly controlled dosimetric approaches. Short LT3 administration suppresses TSH that allows direct targeting of the autonomously functioning thyroid tissue. The three main groups and variants of activity calculation are presented in detail. Calculating the activity allows a 50% average reduction in the ¹³¹I administered dose. Medical strategy should favour the informed patient's choice, after excluding the rare medical causes prompting discussion of an ablative approach. In TFA, low occurrence of hypothyroidism is the rule provided the treatment be given with a TSH < 0.1 mU/L, spontaneously or after LT3 suppression (compensated variety). In GD a long-term remission is rare (< 30%) and should be thoroughly discussed since it leads to euthyroidism in approximately 50% after a 12-year follow-up. Depending on the etiology (GD/TFA) and the 4 clinical goals, ¹³¹I RIT planning is presented with optional choice of a patient adapted method of activity calculation and appropriate management of pharmacological modulators.     

Targeted alpha and beta radiotherapy: An overview of radiopharmaceutical and clinical aspects

For many years, the role of internal radiotherapy has remained limited to certain historical indications such as thyroid cancers or to academic medical research. However, the recent recognition of theranostics and targeted therapies as one of the cornerstones of the modern concept of personalized medicine, has participated in the promotion of new developments for beta and alpha radiotherapy. In this paper, we will review the emerging radionuclides, radiopharmaceutical developments and advances, as well as the clinical successes that have been made in past few years. The results obtained, for some very promising, could herald in a new era for nuclear medicine. However, as presented in this review, in order to fully exploit its potential, and not to remain static as a promising or emerging therapy, the entire field of nuclear medicine must invest in the implementation of well-designed prospective and comparative studies for targeted radiotherapy.     

Enquête nationale en médecine nucléaire : radiopharmaceutiques et activités utilisés en 2007 dans le secteur public

The Institute for radiation protection and nuclear safety (IRSN) and the National institute for health surveillance (InVS) have been collaborating since 2003 to provide updated data on medical exposure of the French population related to medical diagnosis. In this framework, a survey was carried out by IRSN in 2009 within all the 127 departments of nuclear medicine belonging to public hospitals. The rate of participation was high (72% of the departments). The first objective of this survey was to estimate the activity of these nuclear medicine departments (numbers and types of examination, according to their code in the French common classification for medical care). The second objective was to collect data related to the dose delivered to the patient for each type of examination. This article details this second part of the survey and presents, for the 32 most frequent types of examination, the radionuclide used and its chemical form, the average administered activity per examination and the activity range for the responding departments. When a French dose reference level exists, this survey showed that the average administered activity is in agreement with it, excepted for the ^99mTc thyroid scintigraphy with an administered activity close to twice the dose reference level (DRL). The dispersion of administered activity between the departments for a same type of examination depends on the type of examination, and is comprised between 2 and 10 for a 70 kg patient.     

Unusual spread of the follicular thyroid carcinoma,metastases to liver and pancreas

We report a multimetastatic follicular thyroid carcinoma(FTC) with match lesions between ¹⁸F-FDG PET/CT and post-treatment ¹³¹I imaging. The patient had a history of thoracic vertebra corpectomy surgery and liver tru-cut biopsy; both resulted in metastases of FTC. After total thyroidectomy surgery, the patient was referred to the ¹⁸F-FDG PET/CT to investigate other possible metastatic foci. ¹⁸F-FDG PET/CT showed increased FDG uptakes on a cervical lymph node, bones, lung, liver, and pancreas. After treatment of ¹³¹I, post-treatment iodine scintigraphy demonstrated iodine uptakes in the same areas as the ¹⁸F-FDG PET/CT scan and at the thyroid bed. All the matched lesions were concluded as a spread of the FTC. Here we describe an infrequent differentiated thyroid carcinoma case with metastases to the liver and pancreas. This case report also highlights the importance of ¹⁸F-FDG PET/CT in determining the extent of thyroid cancer.     

Dosimetry in molecular nuclear therapy

Advanced personalized dosimetry for molecular nuclear therapy has been shown to be feasible in clinical practice. At the same time instrumentation and dosimetric software are still evolving at a high pace. Procedures developed so far differ in approach and sophistication, and standard operating procedures necessary for accurate patient specific dosimetry do not yet exist. For this reason we restricted ourselves to reviewing the literature and highlighting relevant developments.     

Dosimetry quality control based on percent depth dose rate variation for checking beam quality in radiotherapy

Recently, the quality management inside a radiotherapy department has been crucial to treat cancer efficiently. Thus, many international bodies recommend multiple methods to check in periodically the dosimetry quality beyond the depth of 10 cm as the beam quality index. However, they evade checking out the beam dosimetry quality on both the build-up dose and the electronic equilibrium regions. The objective of this study is to cover the overall variation of the percent depth dose (PDD) by including all sub-regions in the procedure evaluation of the beam quality.In this work, we have studied and examined the dosimetry quality by considering the whole PDD variation. The PDD rate is therefore introduced to determine accurately the quality as an overall notion in external beam radiotherapy according to the field size and photon beam energy. We have presented the reasons and methods to introduce particles contamination, such as electrons and low photon energy in this new approach. The latter enables us to figure the dosimetry quality by extending the International Atomic Energy Agency (IAEA) procedure at any field size less than 25 × 25 cm² under the current conditions without being limited to 10 × 10 cm² on the exponential decay region.     

Impact of Uncertainties in Exposure Assessment on Estimates of Thyroid Cancer Risk among Ukrainian Children and Adolescents Exposed from the Chernobyl Accident

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy⁻¹ (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy⁻¹ (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy⁻¹ (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p = 0.101–0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment.     

Répartiteur de dose des médicaments radiopharmaceutiques : contrôle qualité sur deux sites hospitaliers et comparaison avec la législation en vigueur en France

An increasing number of nuclear medicine departments are equipped with automated measurement systems for the preparation of radiopharmaceuticals, with the main aim of minimising technician's irradiation. However, the automatic measurement of the patient activity differs from the manual measurement in material and method. In this context, the objective of the present study was to test the performances of one of these systems, the Unidose by TRASIS^®, in two newly equipped hospitals. The particularity of these systems is they are made up of two dose calibrators: the entrance calibrator (well chamber) and the exit calibrator (probe). Controls were performed on both of these dose calibrators. The results obtained, as well as the methodology employed, were then compared with the regulatory requirements in France. The results found are coherent between the two sites and have highlighted several non-conformities compared to the current regulations, part of which concerning the carpule dose calibrator, which is actually a probe. These results raise the question of a suitable regulation for the new automated measurement systems in nuclear medicine.     

Pénurie de technétium99m : des pistes pratiques pour gérer les périodes de crise dans les services de médecine nucléaire

Technetium^99m (^99mTc) shortage crisis regularly affect nuclear medicine activity and oblige the community to find solutions in order to perform most of the prescribed exams and avoid systematic substitutions by other non-nuclear medicine techniques. Firstly, some practical solutions can be set up in radiopharmacy departments such as using more than two generators together, realizing fractionated elutions, preparing radiopharmaceuticals with elutions providing from different generators… Then, it could be interesting to have a reflexion in nuclear medicine departments to convene patients the days when ^99mTc supply is sufficient, to pool some exams or to make substitutions with more available isotopes.     

A Feasibility Study of Fricke Dosimetry as an Absorbed Dose to Water Standard for 192Ir HDR Sources

High dose rate brachytherapy (HDR) using ¹⁹²Ir sources is well accepted as an important treatment option and thus requires an accurate dosimetry standard. However, a dosimetry standard for the direct measurement of the absolute dose to water for this particular source type is currently not available. An improved standard for the absorbed dose to water based on Fricke dosimetry of HDR ¹⁹²Ir brachytherapy sources is presented in this study. The main goal of this paper is to demonstrate the potential usefulness of the Fricke dosimetry technique for the standardization of the quantity absorbed dose to water for ¹⁹²Ir sources. A molded, double-walled, spherical vessel for water containing the Fricke solution was constructed based on the Fricke system. The authors measured the absorbed dose to water and compared it with the doses calculated using the AAPM TG-43 report. The overall combined uncertainty associated with the measurements using Fricke dosimetry was 1.4% for k = 1, which is better than the uncertainties reported in previous studies. These results are promising; hence, the use of Fricke dosimetry to measure the absorbed dose to water as a standard for HDR ¹⁹²Ir may be possible in the future.     

Thyroid doses in Ukraine due to 131I intake after the Chornobyl accident. Report II: dose estimates for the Ukrainian population

This paper describes the revision of the thyroid dosimetry system in Ukraine using new, recently available data on (i) revised ¹³¹I thyroid activities derived from direct thyroid measurements done in May and June 1986 in 146,425 individuals; (ii) revised estimates of ¹³¹I ground deposition density in each Ukrainian settlement; and (iii) estimates of age- and gender-specific thyroid masses for the Ukrainian population. The revised dosimetry system estimates the thyroid doses for the residents of the settlements divided into three levels depending on the availability of measurements of ¹³¹I thyroid activity among their residents. Thyroid doses due to ¹³¹I intake were estimated in this study for different age and gender groups of residents of 30,353 settlements in 24 oblasts of Ukraine, Autonomous Republic Krym, and cities of Kyiv and Sevastopol. Among them, dose estimates for 835 settlements were based on ¹³¹I thyroid activities measured in more than ten residents (the first level), for 690 settlements based on such measurements done in neighboring settlements (the second level), and for 28,828 settlements based on a purely empirical relationship between the thyroid doses due to ¹³¹I intake and the cumulative ¹³¹I ground deposition densities in settlements (the third level). The arithmetic mean of the thyroid doses due to ¹³¹I intake among 146,425 measured individuals was 0.23 Gy (median of 0.094 Gy); about 99.8% of them received doses less than 5 Gy. The highest oblast-average population-weighted thyroid doses were estimated for residents of Chernihiv (0.15 Gy for arithmetic mean and 0.060 Gy for geometric mean), Kyiv (0.13 and 0.051 Gy) and Zhytomyr (0.12 and 0.049 Gy) Oblasts followed by Rivne (0.10 and 0.039 Gy) and Cherkasy (0.088 and 0.032 Gy) Oblasts, and Kyiv City (0.076 and 0.031 Gy). The geometric mean of thyroid doses estimated in this study for the entire Ukraine essentially did not change in comparison with a previous estimate, 0.020 vs. 0.021 Gy, respectively. The ratio of geometric mean of oblast-specific thyroid doses estimated in the present study to previously calculated doses varied from 0.51 to 3.9. The highest increase in thyroid doses was found in areas remote from the Chornobyl nuclear power plant with a low level of radioactive contamination: by 3.9 times for Zakarpatska Oblast, 3.5 times for Luhansk Oblasts and 2.9 times for Ivano-Frankivsk Oblast. The developed thyroid dosimetry system is being used to revise the thyroid doses due to ¹³¹I intake for the individuals of post-Chornobyl radiation epidemiological studies: the Ukrainian-American cohort of individuals exposed during childhood and adolescence, the Ukrainian in utero cohort, and the Chornobyl Tissue Bank.

     

Effect of image registration on 3D absorbed dose calculations in 177Lu-DOTATOC peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with ¹⁷⁷Lu or ⁹⁰Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation.A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of ¹⁷⁷Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code.The similarity analysis demonstrated the superiority of the deformable registrations (p < .001).Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [−19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [−67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL.Image based 3D dosimetry for ¹⁷⁷Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.     

Impact dosimétrique des gamma-caméras de nouvelle génération en cardiologie nucléaire

Myocardial perfusion scintigraphy (MPS) has a key role in early detection and prognosis assessment of coronary artery disease. Several recently published studies highlighted the potential future cancer risk associated with SMP, and the cumulative radiation dose over long periods of time due to MPS and additional procedures involving ionizing radiations. This article aims to present a synthesis of recent literature dealing with dosimetry in cardiac imaging procedures, and in particular MPS; to discuss available solutions to reduce as much as possible radiation exposure to patients by applying the principles of justification and optimization; and finally to present the experience of two centers on Nuclear Medicine (Centre Cardiologique du Nord, Saint-Denis and Hôpital Bichat, Paris) about the use of new generation SPECT cameras (CZT) and their impact on dosimetry reduction.     

Thermoluminescence dosimetry of the dose received by scrotum and testes in radiotherapy of rectal cancer,compared to the point doses calculated by 3D-planning software

PurposeRadiation received by the testes in the course of radiotherapy for rectal cancer may cause oligospermia and azospermia. We sought to determine the dose to the scrotum and testes with thermoluminescence dosimetry (TLD), and compare it to the dose calculated by 3D planning software.MethodsThe TLDs were fixed to the scrotum in six points anteriorly and posteriorly in two fractions of radiotherapy. All patients received a 50–50.4 Gy total dose in prone position with 3D-planning. The average dose of TLD measurements was compared to the average of 6 relevant point doses calculated by the planning software.ResultsThe mean scrotal dose of radiation in 33 patients as measured by TLD was 3.77 Gy (7.5% of the total prescribed dose), and the mean of point doses calculated by the planning software was 4.11 Gy (8.1% of the total dose), with no significant difference. A significant relationship was seen between the position of the inferior edge of the fields and the mean scrotal dose (P = .04). Also body mass index (BMI) was inversely related with the scrotal dose (P = .049).ConclusionWe found a dose of about 4 Gy received by the scrotum and testes from a total prescribed dose of 50 Gy in the radiotherapy of rectal carcinoma patients, with TLD measurements confirming testicular dose estimations by the planning software. This dose could be significantly harmful for spermatogenesis. Thus careful attention to the testicular dose in radiotherapy of rectal cancer for men desiring continued fertility is a necessity.     

Quantified 123I-Thyroid Scan based classification of hyperthyroidism

The original thyroid scan (TS) was widely used to identify typical imaging patterns, suggesting the widely accepted main following clinical diagnoses: Grave's disease, Toxic adenoma, [hetero]-nodular goiters and thyroiditis. With the diffusion of sensitive TSH assays, considerable advances in the comprehension of the molecular mechanisms of hormonosynthesis, and new quantification possibilities especially using ¹²³I, the TS is a textbook of molecular imaging. The image can be finely quantified with, not only as regards the Uptake (¹²³IUp) and related parameters but also, the quantification of the spatial targeting leading to a Spatial Target Index (STI). Using this new molecular ¹²³I-TS, TSH values, and when required, correlation to Multiparametric Ultrasounds (MPUS), we generated a basic classification system of hyperthyroidism, with well-defined indexed criteria (C11-1 to C17-3), that allows reporting 24 distinct etiologies. Selected criteria involve TS and contrast patterns, precocious ¹²³IUp (p¹²³IUp), maximal TSH-dependent physiological Uptake, lobar concentration, Uptake and concentration ratios, STI, ^99mTc-MIBI TS and correlative MPUS. This approach allows to identify 4 subtypes of Graves’ disease, including hyperplastic, nodular and common GD variants entangled with Hashimoto's struma, 4 subtypes of Thyroid Functional Autonomy, including Disseminated Functional Autonomy, that cannot be diagnosed with other conventional procedures. Criteria C14-1 to C17-3 report on hyperthyroidism and iodine overload, factitia, main thyroiditis presentations and rare central or tumoral etiologies of hyperthyroidism. This classification, based on ¹²³I-TS molecular imaging, leads to unprecedented diagnostic finesse and paves the way for a personalized theranostic approach in thyroid pathology. Further development towards artificial intelligence networks is under study.