Myriam Monsieurs

The new EANM paediatric dosage card

IntroductionIn a recent publication, Jacobs et al. proposed the use of three tracer-dependent dosage cards for paediatric nuclear medicine.Materials and methodsBased 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.ResultsThe 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.

The Impact of PET and SPECT on Dosimetry for Targeted Radionuclide Therapy

Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for a range of cancers. To date, few treatments have involved the use of dosimetry either to plan treatment or to retrospectively ascertain the absorbed dose delivered during treatment. Also the correlation between absorbed dose and biological effect has been difficult to establish. Tomographic methods permit the determination of the activity volume on a macroscopic scale at different time points. Proper attenuation correction in tomographic imaging requires a patient-specific attenuation map. This can be obtained from scintillation-camera transmission scanning, CT or by using segmented scatter-emission images. Attenuation corrections can be performed either on the projection images, on the reconstructed images, or as part of an iterative reconstruction method. The problem of image quantification for therapy radionuclides, particularly for I-131, is exacerbated by the fact that most cameras are optimised for diagnostic imaging with Tc-99m. In addition, problems may arise when high activities are to be measured due to count losses and mis-positioned events, because of insufficient pile-up and dead time correction methods. Sufficient image quantification, however is only possible if all effects that degrade the quantitative content of the image have been corrected for. Monte Carlo simulations are an appealing tool that can help to model interactions occurring in the patient or in the detector system. This is helpful to develop and test correction techniques, or to help to define detectors better suited to quantitative imaging. PET is probably the most accurate imaging method for the determination of activity concentrations in tissue. PET imaging can be considered for pre-therapeutic treatment planning but ideally requires the use of a radioisotope from the same element as that used for treatment (e.g. I-124 for I-131; Y-86 for Y-90). Problems, however are that--some of the positron emitting isotopes have a shorter half-life--non-standard quantification procedures have to be performed--the availability of the radiopharmaceutical is presently limited; Many 3D-tools and -techniques are now available to the physicist and clinician to enable absorbed dose calculations to both target and critical organs-at-risk. The challenge now facing nuclear medicine is to enable this methodology to be routinely available to the clinic, to ensure common standard operating procedures between centres and in particular to correlate response criteria with absorbed dose estimates.

Clinical radionuclide therapy dosimetry: the quest for the “Holy Gray”

Dear Sir We read with interest the article ‘Clinical radionuclide therapy dosimetry: the quest for the “Holy Gray” ’ [1], which reviewed the use of dosimetry for radionuclide therapy. Whilst both external beam radiotherapy and brachytherapy have seen significant advances in recent decades and are ongoing fields of active research, it is disappointing that some 60 years after the introduction of radioiodine for the treatment of thyroid disorders and cancer [2], there has been little progress in methods for administration of radioactivity in targeted therapy. In contrast to chemotherapy, clinical trials are rare. As a result, radionuclide therapy remains the Cinderella of cancer treatment modalities, with a general opinion in the (nuclear) medicine community that it is under-utilised with respect to more conventional treatments. It is irrefutable that in any form of radiotherapy, the fraction of surviving cells, healthy organ toxicity and tumour response depend primarily on the quantity of energy deposited. Internal dosimetry studies have proved conclusively that fixed administrations can deliver absorbed doses to normal organs, tissues or tumours that vary from patient to patient by an order of magnitude [3–6] Nevertheless, the vast majority of radionuclide treatments are based on the administration of fixed activities or, occasionally, on activities moderated by body weight or body surface area. The logical conclusion from these considerations is that because all patients are treated according to the toxicity limitations dictated by the most vulnerable of patients, the majority of patients are undertreated. By the same token, it is highly probable that in successful therapies a significant number of patients are unnecessarily overtreated. There are several reasons why dosimetry is not routinely implemented. It is often stated that absorbed dose estimates are prone to a large degree of uncertainty. This is undoubtedly true in many cases, although these uncertainties are seldom estimated or quoted in the literature. Accurate image quantification can be attained with adequate data points and with suitable corrections for attenuation and scatter. Tomographic imaging offers greater quantitative accuracy than planar imaging and, as reported by the ICRU [7], it enables inhomogeneous distributions of uptake and absorbed dose to be assessed. To enable direct comparisons and critical appraisal of results from radionuEur J Nucl Med Mol Imaging (2007) 34:1699–1700 DOI 10.1007/s00259-007-0471-9

Estimation of risk based on biological dosimetry for patients treated with radioiodine.

A multicentre study was undertaken to assess the cytogenetic damage to peripheral blood lymphocytes in 31 patients treated with 131I for thyrotoxicosis using the cytokinesis-blocked micronucleus assay. The results were compared to those for eight thyroid carcinoma patients using the same method. For each patient, blood samples were taken immediately before and 1 week after iodine administration. The first blood sample was divided into three fractions and each fraction was subsequently irradiated in vitro with 0, 0.5 and 1 Gy 60Co gamma rays, respectively. After blood culture for 70 h, cells were harvested, stained with Romanowsky-Giemsa and the micronuclei scored in 1000 binucleated cells. For both patient groups, a linear-quadratic dose-response curve was fitted through the data set of the first blood sample by a least squares analysis. The mean increase in micronuclei after 131I therapy (second blood sample) was fitted to this curve and the mean equivalent total body dose (ETBD) calculated. Surprisingly, in view of the large difference in administered activity between thyroid carcinoma patients and thyrotoxicosis patients, the increase in micronuclei after therapy (mean +/- S.D.: 32 +/- 30 and 32 +/- 23, respectively) and the equivalent total body dose (0.34 and 0.32 Gy, respectively) were not significantly different (P > 0.1). The small number of micronuclei induced by 131I therapy (32 +/- 29), compared with external beam radiotherapy for Hodgkins disease (640 +/- 381) or cervix carcinoma (298 +/- 76) [1], gave a cancer mortality estimate of less than 1%. This also explains why late detrimental effects in patients after 131I treatment have not been reported in the literature.

Patient dosimetry after 131I-MIBG therapy for neuroblastoma and carcinoid tumours

Aim The aim of the study was to determine the equivalent total body dose (ETBD) using the cytokinesis-blocked micronucleus assay in 22 131I-meta-iodobenzylguanidine (131I-MIBG) therapies (18 neuroblastoma, mean 5097 MBq, SD 1591; and four carcinoid tumours, mean 7681 MBq, SD 487). The results are correlated with the total body radiation dose according to the Medical Internal Radiation Dosimetry (MIRD) formalism. Methods For each patient, blood samples were taken immediately before and 1 week after 131I-MIBG therapy. The first blood sample was irradiated in vitro with 60Co γ-rays to determine the dose-response curve. Micronuclei were scored in 1000 binucleated cells. By using the dose-response curve the ETBD was derived from the increase in micronuclei after 131I-MIBG therapy (second blood sample). Based on three consecutive biplanar scans taken at 3, 6 and 9 days post-administration respectively, the total body dose following the MIRD formalism was calculated. Results The micronucleus assay was evaluable in only 14 out of 22 131I-MIBG therapies due to cell division inhibition caused by previous chemotherapy treatments and lymphocyte dilution due to blood transfusions given shortly after 131I-MIBG therapy. For these 14 therapies, the mean micronucleus yield after 131I-MIBG therapy was significantly increased (P<0.01) with a mean of 92 (SD 77) for neuroblastoma patients and with a mean of 35 (SD 8) for carcinoid patients. The increase observed in the present study is greater than previously observed after 131I therapy and 89Sr therapy but much lower than after external beam radiotherapy. For all patients treated with multiple therapies, the initial increase in micronucleus yield had at least partially recovered by the time of the next therapy. This might be explained by an increased turnover of lymphocytes. A mean ETBD of 0.95 Gy (SD 0.55) for neuroblastoma patients and a mean of 0.46 Gy (SD 0.09) for carcinoid patients was calculated. A reasonable correlation (R = 0.87) between the ETBD and the MIRD dose was obtained. The slope value of 0.75 can be explained by the low dose rate effect. Conclusions The observation in the present study of important inter-individual variability in the total body dose, with the possibility of high dose values, suggests the necessity of individual dosimetry when administering 131I-MIBG therapy, especially considering that generally more than one therapy is given to each patient.

201Tl scintigraphy does not allow visualization of the thyroid in euthyroid and hyperthyroid patients treated with amiodarone

A retrospective study was performed to evaluate the usefulness of thallium scintigraphy for visualization of thyroid morphology and function. Moreover, applying absolute quantitation, we wished to confirm the qualitatively reduced 99Tc(m) uptake reported by Wiersinga et al. in both euthyroid and hyperthyroid patients treated with amiodarone. Over a period of 2 years (1995-96), 10 patients (group A; 2 females, 8 males, mean age 68.6 years, range 61-74 years) receiving amiodarone treatment for cardiac arrhythmias for at least 4 months were referred for exploration of either hyperthyroidism (n = 4) or for exclusion of parathyroid adenoma (n = 6). During the same period, 17 patients (group B; 10 females, 7 males, mean age 62 years, range 19-91 years) referred for Tc-Tl subtraction scintigraphy, and in whom follow-up revealed no thyroid or parathyroid pathology, were used as controls. In all patients, thyroid status was assessed by thyroid function tests. 201Tl and 99Tc(m) uptake was calculated as a percentage of the injected dose, taking account of net injected counts and background and isotope decay correction. Original images were scored using a 2-point scoring system (0 = poor, 1 = fair or good). Uptake of both 99Tc(m) and 201Tl was significantly reduced in group A (99Tc[m]: 0.16 +/- 0.21%; 201Tl: 0.30 +/- 0.21%; mean +/- S.D.) compared to group B (99Tc[m]: 1.58 +/- 1.07%; 201Tl: 0.72 +/- 0.37%) (P < 0.005). The mean relative reduction in 99Tc(m) uptake was more pronounced (90% decrease) than that of 201Tl (58% decrease). In group A, the 99Tc(m) and 201Tl image quality was poor in 10 of 10 and 8 of 10 patients respectively. In group B, the 99Tc(m) and 201Tl image quality was poor in 3 of 17 and 4 of 17 patients respectively. The decreased uptake of 201Tl may reflect the inhibitory effect of iodides on adenyl cyclase and its stimulation by TSH. In conclusion, the data presented confirm the qualitatively reduced pertechnetate uptake reported by Wiersinga et al. Furthermore, 201Tl uptake by the thyroid in euthyroid or hyperthyroid patients treated with amiodarone is also reduced. Although quantitatively less pronounced, it does not allow proper visualization of the thyroid.

Physical evaluation of 511 keV imaging with gamma camera and PET

This work presents an evaluation of a gamma camera operating in coincidence mode. The major limitations of these cameras compared to full-ring PET are the limited count rate and sensitivity. The authors evaluate the progress in count rate which was made by upgrading the system with new electronics. At the moment most gamma cameras use septa to limit the axial acceptance angle for coincidences. Sensitivity can be improved by removing the septa, which results in a fully 3D acquisition. The improvements in sensitivity are measured. Another limitation is the non-uniform sensitivity due to the varying acceptance angle, which decreases linearly from the center towards the edges in a 180/spl deg/ opposed dual head configuration. Sensitivity and uniformity can be improved by going from a dual head to a triple head configuration. As triple head coincidence is not yet available, the authors calculated the theoretical sensitivity profiles from geometrical considerations.

The Removal, Transportation and Final Treatment and Conditioning of the THETIS Research Reactor Spent Fuel of the University of Ghent (Belgium) Achieved in 2010

The THETIS research reactor on the site of the Nuclear Sciences Institute of the Ghent University has been in operation from 1967 until December 2003. This light-water moderated graphite-reflected low-enriched uranium pool-type reactor has been used for various purposes e.g. the production of radio-isotopes and activation analyses. During the first years its core power was 15 kW. In the early ’70, a core enlargement allowed for operation at typically 150 kW, while the maximum was allowed to be 250 kW. The fuel was 5% enriched uranium cladded with AISI304L stainless steel, with graphite plugs at both ends of the tubes. In order to decommission the reactor, the spent fuel and other nuclear materials present had to be removed from the reactor site. Ghent University entrusted SCK·CEN, the Belgian Nuclear Research Centre, with the study of the further management of the spent fuel. Various options such as reprocessing, intermediate storage awaiting final disposal were investigated. However the characteristics and the small amount of spent fuel (84.64 kg of UO2 ) made these solutions very expensive. In the meantime ONDRAF/NIRAS, the Belgian radioactive waste management agency, was developing together with Belgoprocess, a solution for final conditioning in 400 liter drums and further intermediate storage of the spent fuel in its nuclear facilities at the BELGOPROCESS site in Dessel. This conditioned waste is foreseen to enter the future geological disposal site after the intermediate storage period only after 2050. Finally SCK·CEN recommended this solution for the back-end of the THETIS spent fuel and Ghent University declared this spent fuel as radioactive waste. Once the feasibility for conditioning and storage was demonstrated, further actions were taken in order to unload the spent fuel out of the reactor and to transport it to the PAMELA-installation at the Belgoprocess site in Dessel. Finally after receiving all necessary licensing authorisations from the FANC/AFCN, the Belgian nuclear safety authority, the operations started at the reactor site beginning of 2010 and the spent fuel was placed into the intermediate storage building after conditioning at the Belgoprocess site at the end of 2010. The paper will focus on: - the inventarisation and characterization of the spent fuel and other nuclear materials; - the operations at Ghent University and Belgoprocess sites; - the conclusions drawn from the operations.Copyright