Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary?

In radionuclide therapy with iodine-131 labelled pharmaceuticals, free (131)I may be released and trapped by the thyroid, causing an undesirable radiation burden. To prevent this, stable iodide such as potassium iodide (KI) can be given to saturate the thyroid before (131)I is administered. The guidelines of the European Association of Nuclear Medicine do not, however, recommend special precautions when administering (131)I-lipiodol therapy for hepatocellular carcinoma. Nevertheless, some authors have reported (131)I uptake in the thyroid as a consequence of such therapy. In this study, the influence of prophylactic KI on the thyroid uptake and dose (MIRD dosimetry) was prospectively investigated. (131)I-lipiodol was given as a slow bolus selectively in the proper hepatic artery or hyperselectively in the right and/or left hepatic artery. Patients were prospectively randomised into two groups. One group received KI in a dose of 100 mg per day starting 2 days before (131)I-lipiodol administration and continuing until 2 weeks after therapy (KI group; n=31), while the other group received no KI (non-KI group; n=37). Thyroid uptake was measured scintigraphically as a percentage of administered activity 7 days after (131)I-lipiodol ( n=68 treatments). The absorbed radiation dose to the thyroid was assessed by scintigraphy after 7 and 14 days using a mono-exponential fitting model and MIRD dosimetry ( n=40 treatments). The mean activity of (131)I-lipiodol administered was 1,835 MBq in a volume of 2 ( n=17) or 4 ( n=51) ml. Thyroid uptake was lower in the KI group, being 0.23%+/-0.06% of injected activity ( n=31) compared with 0.42%+/-0.20% in the non-KI group ( n=37); the mean thyroid dose was 5.5+/-1.6 Gy in the KI group ( n=19) versus 11.9+/-5.9 Gy in the non-KI group ( n=21). These differences were statistically significant ( P<0.001). No effect of the amount of added cold lipiodol (4 vs 2 ml total volume) or selectivity of (131)I-lipiodol administration was evident ( P>0.1). (131)I-lipiodol is associated with a generally low thyroid uptake and dose that may be significantly decreased by KI premedication. Given the low cost and the very good tolerance of the KI treatment, we believe the use of KI should be recommended in the majority of the patients.

Translocation frequencies measured in patients one year after radioactive iodine therapy for thyrotoxicosis.

PURPOSE: To investigate the incidence of translocations induced by iodine-131 therapy in thyrotoxicosis patients 1 year after the administration of the radiolabelled compound. MATERIALS AND METHODS: Tricolour FISH with whole-chromosome-specific probes for chromosomes 2, 4 and 8 was used for scoring translocations. From the genomic translocation frequencies, derived using the Lucas formula, equivalent whole-body doses were calculated, based on the in vitro (60)Co gamma-ray dose-response curve. RESULTS: A total of 101 translocations were observed in 4864 metaphases, 63% being of the two-way type. In the control group used for obtaining dose-response data, nine translocations were observed in 5278 metaphases, 55% being two-way translocations. No correlation was found between the observed frequency of translocations and administered radioactivity. Using the in vitro dose-response, an estimated average dose for the group of nine patients of 0.79 +/- 0.22Gy was obtained. Compared with frequencies following the assumption that the involvement of a particular chromosome in a two-break exchange-type aberration is proportional to its DNA content, chromosome 4 was more frequently involved and chromosomes 2 and 8 less frequently involved in chromosomal rearrangements. CONCLUSION: This study shows that (131)I therapy for thyrotoxicosis patients induced translocations, especially in chromosome 4, which could be detected 1 year after the administration of the radiolabelled compound.

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 22 131 I-meta-iodobenzylguanidine (131 I-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 gamma-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.

Dosimetry from organ to cellular dimensions.

While the conventional Medical Internal Radiation Dose (MIRD) approach is useful for estimating approximate organ absorbed doses in diagnostic applications of isotopes, this strategy is suited neither to the exacting requirements of targeted radionuclide therapy nor to radiopharmaceuticals with a non-uniform activity distribution. For the individual treatment planning of patients treated with common radionuclides emitting high energy betas, the individual activity distribution has to be obtained from CT-SPECT images and the doses to the target organs and critical tissues have to be calculated by point-kernel methods. Due to the stochastic nature, alpha-radioimmunotherapy (alpha-RIT) requires microdosimetric calculations with Monte Carlo on a realistic model of the source and target tissue at the micrometer level. For a prediction of the biological effects of intracellular labelling with Auger electron emitters an accurate subcellular modelling including the DNA structure at the nanometre level with knowledge of the target for the considered biological effect is necessary.

Adaptive response in patients treated with 131I.

UNLABELLED: The aim of this study was to investigate whether an adaptive response (defined as the induction of radiation tolerance after a small dose of radiation) could be observed in peripheral blood lymphocytes of patients treated with 1311 for thyroid disease. METHODS: For each patient, blood samples were taken immediately before and 1 wk after 131I administration. Each blood sample was divided into 3 fractions and the fractions were subsequently irradiated in vitro with 0, 0.5, and 1.0 Gy 60Co gamma-rays. After blood culture for 70 h, cells were harvested and stained with Romanowsky-Giemsa and micronuclei were counted in 1000 binucleated cells. The increase in micronuclei by the in vitro irradiation of the blood samples taken before and after therapy was compared. In this setup, an adaptive response is represented by a significant decrease of the in vitro induced micronucleus yield after therapy compared with that before therapy. The iodine therapy can be considered as an in vivo adaptation dose, after which the subsequent in vitro irradiation acts as a challenge dose. To investigate the reproducibility of the method, 2 subsequent blood samples of healthy volunteers were taken 7 d apart. Irradiation and cell culture were performed as described. RESULTS: In 8 of 20 patients, a significant (P = 0.0002) decrease was found in the in vitro induced micronucleus yield in the blood sample taken 1 wk after 1311 administration compared with that of the blood sample taken before therapy. No significant (P > 0.1) differences were observed between these 8 patients and the other patients when the number of micronuclei induced in vivo by the iodine treatment and the resulting equivalent total body dose were compared. None of the control subjects showed a significant change in micronucleus yield after in vitro irradiation between both blood samples taken 1 wk apart. CONCLUSION: The iodine treatment can act as an in vivo adaptation dose and can induce an adaptive response that is observed by a decrease of the cytogenetic damage in peripheral blood lymphocytes after in vitro irradiation as a challenge dose. A large interindividual difference was observed.

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 Hodgkin's 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.

Real-life radiation burden to relatives of patients treated with iodine-131: a study in eight centres in Flanders (Belgium).

In view of the EURATOM 96/29 [1] regulations, a prospective multicentre study was performed to evaluate the present guidelines given to relatives of patients treated with iodine-131 for both thyroid carcinoma and thyrotoxicosis, based on the real-life radiation burden. This study comprised 166 measurements carried out on a group of 94 relatives of 65 patients. All relatives wore a thermoluminescent dosemeter (TLD) on the wrist for 7 days. Sixty-one relatives agreed to wear another TLD for an additional 7 days. TLD were placed on nine patients' bedside tables. The eight participating centres were arbitrarily divided into three groups according to the period of time they advised their patients to sleep separately. Groups I, II and III respectively advised their patients to sleep separately for 0, 7-10 and 14-21 days. The median dose received by in-living relatives of thyroid carcinoma patients during the 14 days following hospital discharge was 281 microSv (doses to infinity not calculated); the median dose to infinity received by in-living relatives of ambulatory treated thyrotoxicosis patients was 596 microSv, as compared with 802 microSv for in-living relatives of hospitalised thyrotoxicosis patients. In general the children of patients received a significantly (P < 0.1) lower mean dose than their partners. For thyroid carcinoma patients, only two relatives out of 19 (10%) exceeded the EURATOM 96/29 limit of 1 mSv/year. For thyrotoxic patients, 28% of relatives exceeded the EURATOM 96/29 limit, but none of them were relatives of patients who followed guidelines for 21 days. The results of this study indicate that sleeping separately for 7 days, after a period of hospitalisation of 2-3 days, will usually be sufficient for thyroid carcinoma patients. For thyrotoxicosis patients, up to 21 days of sleeping separately could be necessary in order to strictly abide by EURATOM 96/29. Therefore, the authors propose the implementation of a non-rigid dose constraint for people who "knowingly and willingly" help patients treated with 131I, while still following the ALARA principle.

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.

Bordetella hinzii sp. nov., isolated from poultry and humans.

A polyphasic taxonomic study that included DNA-rRNA hybridizations, DNA-DNA hybridizations, DNA base ratio determinations, whole-cell protein and fatty acid analyses, and an examination of classical phenotypic characteristics was performed in order to classify human and veterinary isolates that resemble Bordetella avium. Twelve poultry isolates and two human isolates were assigned to a new species, for which we propose the name Bordetella hinzii. The position of this organism in the family Alcaligenaceae and various genotypic, phenotypic, and chemotaxonomic characteristics are described.