Breast cancer risk among thyroid cancer survivors and the role of I-131 treatment.

BACKGROUND: Female thyroid cancer survivors are more likely to have a higher risk of breast cancer compared to the general population, and the underlying causes are yet to be understood. The potential role of I-131 treatment on this association remains controversial. METHODS: We pooled individual data of women who were treated for differentiated thyroid cancer from 1934 to 2005 in France, Italy and Sweden. Standardized incidence ratios (SIRs) for breast cancer were estimated by comparison with age, sex and calendar-year expected values of the general population in each country. We estimated breast cancer risk in relation to I-131 treatment using time-dependent Poisson models. RESULTS: Of 8475 women (mean age at diagnosis: 45 years, range 2-90 years), 335 were diagnosed with breast cancer [SIR = 1.52, 95% confidence interval (CI): 1.36-1.69] during a median follow-up time of 12.7 years since diagnosis. Overall, breast cancer risk did not differ between women treated or not with I-131 (relative risk=1.07, 95% CI 0.84-1.35). However, breast cancer risk increased with increasing cumulative I-131 activity, without significant departure from linearity (excess relative risk per 100 mCi=17%, 95% CI: 2% to 38%). The higher risk associated with a cumulative I-131 activity of ≥100 mCi and ≥400 mCi was translated into 4 (95% CI -4 to 13) and 42 (95% CI -8 to 93) excess breast cancer cases per 10,000 person-years, respectively. CONCLUSIONS: An elevated risk was observed for the highest cumulative administered activity (>=400 mCi), and a significant dose-dependent association was observed among thyroid cancer survivors who were treated with I-131. However, overall, I-131 treatment might only explain partly the increase in breast cancer risk among female thyroid cancer survivors.

Redifferentiation of a BRAFK601E-Mutated Poorly Differentiated Thyroid Cancer Patient with Dabrafenib and Trametinib Treatment.

A 59-year-old woman with locally invasive poorly differentiated thyroid cancer with synchronous lung, mediastinal, and bone metastases and a somatic BRAFK601E mutation with contraindication for antiangiogenic drugs was treated with dabrafenib and trametinib. During treatment, serum levels of thyroglobulin increased as early as day 7 up to 10-fold over baseline at week 4. Concurrently, clinical hyperthyroidism occurred, with free triiodothyronine and free thyroxine levels increasing to 6.6 and 4.4 times their upper reference limit. Fludeoxyglucose positron emission tomography/computed tomography at one and two months after treatment initiation showed a PERCIST metabolic response with a 82% decrease in fludeoxyglucose uptake, whereas disease remained morphologically stable according to RECIST criteria. A diagnostic radioactive iodine whole-body scan performed when the patient was thyrotoxic with an undetectable serum thyrotropin level, in the absence of any exogenous thyrotropin stimulation, showed high radioactive iodine uptake in the lung, mediastinum, and skull metastases. A biopsy performed two months after treatment initiation showed a more differentiated growth pattern and a decrease in the mitotic activity compared to baseline. An increase of thyroglobulin and thyroid peroxidase was observed at both the protein and mRNA levels. Sodium-iodide symporter mRNA expression increased by >750 times over its initial level, and sodium-iodide symporter protein expression became detectable under treatment. A decrease in general status due to thyrotoxicosis led to treatment discontinuation. Thyrotoxicosis resolved rapidly and radioactive iodine uptake decreased by >90%. This clinical case shows that redifferentiation itself is not necessarily associated with an antitumor effect.

The intensity of 18FDG uptake does not predict tumor growth in patients with metastatic differentiated thyroid cancer.

PURPOSE: In patients with metastatic differentiated thyroid carcinoma (DTC), fluorodeoxyglucose (FDG) uptake as well as age, tumor size and radioactive iodine (RAI) uptake are prognostic factors for survival. High FDG uptake is a poor prognostic factor and lesions with high FDG uptake are often considered aggressive, but the predictive value of FDG uptake for morphological progression is unknown. The principal aim of this retrospective single center study was to determine whether the intensity of FDG uptake was correlated on a per lesion analysis with tumor growth rate (TGR) expressed as the percentage of increase in tumor size during 1 year (1-year TGR). METHODS: Fifty five patients with DTC were included between July 2012 and May 2014 with the following criteria: (i) at least one distant metastasis measuring ≥ 1 cm in diameter on CT scan (ii) evaluation by FDG-positron emission tomography/computed tomography (PET/CT) performed at our center (iii) at least one CT or another FDG-PET/CT performed 3 to 12 months after the reference FDG-PET/CT in the absence of systemic or local treatment between the two imaging procedures. RESULTS: One hundred and fifty-six metastatic lesions located in lungs (63), neck lymph nodes (28), chest lymph nodes (42), bone (11), liver (2) and other sites (12) were studied. The median size was 16 mm, median SUVmax/lesion: 8.7; median metabolic tumor volume/lesion (Metab.TV/lesion): 3.7 cm3. The median 1-year TGR was 40.68 %. SUVmax and Metab.TV/lesion were not correlated to their 1-year TGR (p = 0.38 and p = 0.74 respectively). Among single patients with multiple lesions, the lesions with the highest SUVmax/lesion or the highest Metab.TV/lesion did not disclose the higher 1-year TGR. CONCLUSION: The intensity of FDG uptake on a per lesion analysis is not correlated to its 1-year TGR and cannot be used as a surrogate marker of tumour progression.

[Potential radiation hazard in nuclear medicine]. / Risques liés à la médecine nucléaire diaqnostique et thérapeutique.

Nuclear medicine uses unsealed radioisotopes. The potential radiation hazards depend on the amount of radioactivity administered and the type of radionucleide. Thus, radiation safety instructions will minimize radiation exposure and contamination as low as reasonably achievable. National nuclear safety authority requires rules, regulations and exposure limits for both patients and workers. Good practices and training staff contribute to optimize the radioprotection.

Strategies of radioiodine ablation in patients with low-risk thyroid cancer.

BACKGROUND: It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care. METHODS: In our randomized, phase 3 trial, we compared two thyrotropin-stimulation methods (thyroid hormone withdrawal and use of recombinant human thyrotropin) and two radioiodine ((131)I) doses (i.e., administered activities) (1.1 GBq and 3.7 GBq) in a 2-by-2 design. Inclusion criteria were an age of 18 years or older; total thyroidectomy for differentiated thyroid carcinoma; tumor-node-metastasis (TNM) stage, ascertained on pathological examination (p) of a surgical specimen, of pT1 (with tumor diameter ≤1 cm) and N1 or Nx, pT1 (with tumor diameter >1 to 2 cm) and any N stage, or pT2N0; absence of distant metastasis; and no iodine contamination. Thyroid ablation was assessed 8 months after radioiodine administration by neck ultrasonography and measurement of recombinant human thyrotropin-stimulated thyroglobulin. Comparisons were based on an equivalence framework. RESULTS: There were 752 patients enrolled between 2007 and 2010; 92% had papillary cancer. There were no unexpected serious adverse events. In the 684 patients with data that could be evaluated, ultrasonography of the neck was normal in 652 (95%), and the stimulated thyroglobulin level was 1.0 ng per milliliter or less in 621 of the 652 patients (95%) without detectable thyroglobulin antibodies. Thyroid ablation was complete in 631 of the 684 patients (92%). The ablation rate was equivalent between the (131)I doses and between the thyrotropin-stimulation methods. CONCLUSIONS: The use of recombinant human thyrotropin and low-dose (1.1 GBq) postoperative radioiodine ablation may be sufficient for the management of low-risk thyroid cancer. (Funded by the French National Cancer Institute [INCa] and the French Ministry of Health; ClinicalTrials.gov number, NCT00435851; INCa number, RECF0447.).

Thyroid cancer patients treated with 131I: radiation dose to relatives after discharge from the hospital.

BACKGROUND: Thyroid cancer patients treated with radioiodine are potential source of radiation exposure for other individuals. Thus, we evaluated the radiation dose received by family members of thyroid cancer patients treated with (131)I after hospital discharge. MATERIALS AND METHODS: Seventy-six family members of 56 thyroid cancer patients were included in the study. Thyroid cancer patients were given 3.7 GBq of (131)I and remained in a radiation protection ward for 3 days. Radiation protection recommendations were given to patients and relatives. Life conditions were recorded and radiation doses were monitored using a personal dosimeter. RESULTS AND DISCUSSION: At discharge, the mean residual activity was 188 MBq. The mean radiation dose delivered to relatives during the 7 days after discharge was low (51.5 µSv) and was similar with either recombinant human thyrotropin (rhTSH) (59 µSv) or withdrawal (50 µSv) (p = 0.37). CONCLUSION: With our current practice, radiation doses to relatives are low and well below international recommendations.

Evaluation of a trainer phantom in the learning phase of sentinel lymph node identification in breast cancer.

BACKGROUND: The concept of a learning phase is difficult to implement in a university setting, as it is unacceptable to subject a patient who requires only lymphadenectomy to axillary dissection for the purpose of training surgeons. We therefore sought to evaluate intraoperative sentinel node detection using a phantom, the Senti-Trainer. Learning phases on the Senti-Trainer and detection rate were assessed in order to determine whether the proficiency of surgeons in training improved with the number of procedures. METHODS: Twenty residents each performed 30 detection procedures of a sentinel node on the silicon phantom. Each resident was evaluated at each procedure, and an observation report was made every five procedures. Evaluation was single-blind as the surgeons did not know the result of the previous detection and were aware of the results only after the thirtieth procedure. RESULTS: The mean detection rate was 75% during the first procedure and reached 95% (or 5% detection errors) at the 30th procedure (p<0.0001; OR=6.33 with a 95% CI=[2.31; 17.33]). Proficiency in sentinel lymph node (SLN) identification also increased with the number of procedures performed. The ability to localize SLN improved during the learning phase with the increasing number of procedures performed. Mean detection time during the 30 procedures was 150 s (range: 115-210 s). CONCLUSIONS: Training on a phantom showed that this is a valuable teaching tool that enables surgeons to become familiar with gamma probes. It cannot replace the clinical training phase, but is an important aid to proficiency in intraoperative detection.

Health outcomes of children fathered by patients treated with radioiodine for thyroid cancer.

CONTEXT AND OBJECTIVES: Radiation is known to be mutagenic. The present study analyses birth outcomes and the health of offspring from men previously exposed to (131) I treatment for thyroid carcinoma. METHODS: Data on 493 pregnancies (356 from 173 untreated fathers, 23 from 17 patients who have undergone surgery alone and 114 from 63 fathers who received (131) I) were obtained by interviewing male patients treated for thyroid carcinoma who had not received significant external radiation to the testes. Among these pregnancies, 73 were conceived from fathers who had received more than 370 MBq. RESULTS: The mean activity for the 114 pregnancies fathered by 63 patients was 3993 MBq leading to an estimated radiation dose of 9.2 cGy to the testes (MIRD committee coefficient). No significant differences between untreated and treated fathers were found for any adverse outcome. CONCLUSION: There was no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring, whatever the event considered. As our study is underpowered, the question of whether testicular irradiation, fractionated or not, is linked to impaired fertility or consequences on offspring remains to be established.

131I effective half-life and dosimetry in thyroid cancer patients.

UNLABELLED: (131)I treatment in thyroid cancer patients may induce side effects, including extrathyroidal cancer and leukemia. There are still some uncertainties concerning parameters that may influence the effective half-life of (131)I and the absorbed doses by extrathyroidal organs. METHODS: Whole-body retention of radioiodine was measured in 254 patients, and repeated quantitative whole-body scans and measurements of the urinary excretion of (131)I were performed on 30 of these patients. RESULTS: The mean effective half-life (10.5 h) was shorter by 31%, with little difference between patients, in the 36 patients who received recombinant human thyroid-stimulating hormone than in the 218 patients who underwent thyroid hormone withdrawal (15.7 h). The residence times in the stomach and in the rest of the body were significantly shorter in patients who received recombinant human thyroid-stimulating hormone than in patients who underwent withdrawal, but the residence times were similar in the colon and bladder. CONCLUSION: In patients who undergo thyroid hormone withdrawal, the longer mean effective half-life is mainly due to delayed renal excretion of (131)I and results in dose estimates higher than the data in report 53 of the International Commission on Radiological Protection, which were obtained from healthy, euthyroid subjects.

Therapeutic administration of 131I for differentiated thyroid cancer: radiation dose to ovaries and outcome of pregnancies.

UNLABELLED: Radiation is known to be mutagenic. The present study updates a 10-y-old study regarding pregnancy outcome and the health of offspring of women previously exposed to radioiodine ((131)I) during thyroid carcinoma treatment, by doubling the number of pregnancies that occurred after exposure. METHODS: Data on 2,673 pregnancies were obtained by interviewing female patients who were treated for thyroid carcinoma but had not received significant external radiation to the ovaries. RESULTS: The incidence of miscarriages was 10% before any treatment for thyroid cancer; this percentage increased after surgery for thyroid cancer, both before (20%) and after (19%) (131)I treatment, with no variation according to the cumulative dose. In contrast to previously reported data, miscarriages were not significantly more frequent in women treated with radioiodine during the year before conception, not even in women who had received more than 370 MBq during that year. The incidences of stillbirths, preterm births, low birth weight, congenital malformations, and death during the first year of life were not significantly different before and after (131)I therapy. The incidences of thyroid and nonthyroid cancers were similar in children born either before or after the mother's exposure to radioiodine. CONCLUSION: There is no evidence that exposure to radioiodine affects the outcomes of subsequent pregnancies and offspring. The question as to whether the incidences of malformations and thyroid and nonthyroid cancers are related to gonadal irradiation remains to be established. The doubling dose is still being heatedly debated, and the value of 1 Gy as the doubling dose in humans should be reevaluated.

Imaging of the distribution of (90)y-ibritumomab tiuxetan in bone marrow and comparison with pathology.

PURPOSE: Radioimmunotherapy with anti-CD20 antibodies (Abs) labeled with beta-emitters is now used in the treatment of non-Hodgkin's lymphoma (NHL). Because (90)Y is a pure beta-emitter, no direct image of its distribution can be obtained in humans. In this paper, we present in this study imaging data of (90)Y-Ab distribution in human-mantle-cell lymphoma within a mouse model. Describing the actual distribution of the radionuclide at the level of particles range may have important impact on patient dosimetry and therapy treatment planning. EXPERIMENTAL DESIGN: NOD/SCID mice were grafted with a human NHL cell line that involves the bone marrow. The mice were treated with (90)Y-ibritumomab tiuxetan (Zevalin); Schering AG, Germany) and sacrificed 2 hours after Zevalin administration. Tissue sections were then prepared and viewed under conventional microscopy. The distribution of the radioactivity in mouse femur was determined by using digital autoradiography and subsequently correlated with immunohistochemical results. RESULTS: Various extent of bone marrow infiltration was investigated and found to be reproducible. Zevalin uptake was heterogeneous within the bone marrow. However, unspecific mouse monoclonal uptake by accessory myeloid cells gave nonspecific background radioactivity. Treating mice with an irrelevant mouse IgG1 monoclonal antibody (mAb) before Zevalin injection controlled this unspecific uptake, and images were strongly correlated with bone marrow infiltration on histologic analysis. CONCLUSIONS: Our model was reproducible, and allows for the study of various bone marrow involvement with good sensitivity. We demonstrated that imaging of the beta-emitter was possible with good image quality and that (90)Y-Zevalin is distributed heterogeneously within bone marrow. These data suggest that detailed pharmacokinetics may be developed with this model.

How the availability of recombinant human TSH has changed the management of patients who have thyroid cancer.

Recombinant human TSH (rhTSH) is used in patients who have had surgery for thyroid cancer but are at low risk of recurrence. The rhTSH is used for the preparation of postoperative administration of 3.7 GBq (100 mCi) of radioiodine for thyroid-remnant ablation and for the determination of serum thyroglobulin levels during follow-up. In these two conditions, the efficiencies of levothyroxine withdrawal and rhTSH administration are similar; however, rhTSH can be administered during levothyroxine treatment, and its use avoids the hypothyroid period induced by levothyroxine withdrawal, reduces whole body exposure after radioiodine administration, avoids potential morbidity and maintains a better quality of life compared with hormone withdrawal.

Radiation and inhibition of angiogenesis by canstatin synergize to induce HIF-1alpha-mediated tumor apoptotic switch.

Tumor radioresponsiveness depends on endothelial cell death, which leads in turn to tumor hypoxia. Radiation-induced hypoxia was recently shown to trigger tumor radioresistance by activating angiogenesis through hypoxia-inducible factor 1-regulated (HIF-1-regulated) cytokines. We show here that combining targeted radioiodide therapy with angiogenic inhibitors, such as canstatin, enhances direct tumor cell apoptosis, thereby overcoming radio-induced HIF-1-dependent tumor survival pathways in vitro and in vivo. We found that following dual therapy, HIF-1alpha increases the activity of the canstatin-induced alpha(v)beta(5) signaling tumor apoptotic pathway and concomitantly abrogates mitotic checkpoint and tetraploidy triggered by radiation. Apoptosis in conjunction with mitotic catastrophe leads to lethal tumor damage. We discovered that HIF-1 displays a radiosensitizing activity that is highly dependent on treatment modalities by regulating key apoptotic molecular pathways. Our findings therefore support a crucial role for angiogenesis inhibitors in shifting the fate of radiation-induced HIF-1alpha activity from hypoxia-induced tumor radioresistance to hypoxia-induced tumor apoptosis. This study provides a basis for developing new biology-based clinically relevant strategies to improve the efficacy of radiation oncology, using HIF-1 as an ally for cancer therapy.

Whole-body distribution and radiation dosimetry of the dopamine transporter radioligand [(11)C]PE2I in healthy volunteers.

INTRODUCTION: This study reports on the biodistribution and radiation dosimetry of a cocaine analog, the (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (PE2I), labeled with carbon 11 ([(11)C]PE2I). [(11)C]PE2I is used in positron emission tomography (PET) for examination of the dopamine neuronal transporter (DAT). DAT radioligands are often used to evaluate the progression of Parkinson's disease or the efficiency of neuroprotective therapeutics, and, typically, these studies required several successive PET scans. METHODS: In three healthy male volunteers, whole-body scans were performed up to 2 h following intravenous injection of 321+/-6 MBq of [(11)C]PE2I. For each subject, regions of interest were defined over all visible organs to generate time-activity curves and calculate the percentage of injected activity. Time-activity data were fitted to a monoexponential model, as an uptake phase followed by a mono-exponential washout, or bi-exponential model to obtain residence times. With the use of the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. RESULTS: Blood pressure and ECG findings remained unchanged after radioligand injection. The primary route of clearance was renal. Ten minutes after injection, high activities were observed in the kidneys, urinary-bladder, stomach, liver, salivary glands and brain. The urine bladder wall, stomach and liver received the highest absorbed doses. The average effective dose of [(11)C]PE2I was estimated to be 6.4+/-0.6 microSv/MBq. CONCLUSION: The amount of [(11)C]PE2I required for adequate DAT PET imaging results in an acceptable effective dose equivalent permitting two or three repeated cerebral PET studies, with the injection of 222 MBq for each study.

Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal.

UNLABELLED: Technical aspects and results of the dosimetric assessments of postoperative radioiodine ablation in the framework of an international, prospective, controlled, randomized, comparative study of the effectiveness of ablation therapy with 3.7 GBq (131)I in differentiated thyroid cancer after stimulation with recombinant human TSH (rhTSH) or by thyroid hormone withdrawal (THW) are presented. METHODS: Sixty-three patients were randomized after thyroidectomy to either the THW or the rhTSH group. Scintigraphic neck images were acquired starting 48 h after radioiodine administration to assess biokinetics in the thyroid remnant. The activity in blood samples was quantified and data from whole-body probe measurements and scintigraphic whole-body scans were combined to deduce retention curves in blood and whole body, respectively. The absorbed dose to the blood was calculated using a modified approach based on the formalism of the MIRD Committee of the Society of Nuclear Medicine. RESULTS: The effective half-time in the remnant thyroid tissue was significantly longer after rhTSH than THW (67.6 +/- 48.8 vs. 48.0 +/- 52.6 h, respectively; P = 0.01), whereas the observed differences of the mean 48-h (131)I uptakes (0.5% +/- 0.7% vs. 0.9% +/- 1.0% after THW; P = 0.1) and residence times (0.9 +/- 1.3 vs. 1.4 +/- 1.5 h after THW; P = 0.1) between the rhTSH and THW groups were not statistically significant. The specific absorbed dose to the blood was significantly (P <0.0001) lower after administration of rhTSH (mean, 0.109 +/- 0.028 mGy/MBq; maximum, 0.18 mGy/MBq) than after THW (mean, 0.167 +/- 0.061 mGy/MBq; maximum, 0.35 mGy/MBq), indicating that higher activities of radioiodine might be safely administered after exogenous stimulation with rhTSH. CONCLUSION: Indication of an influence of the residence time of radioiodine in the blood on the fractional uptake into thyroid remnant was found. A novel regimen is proposed in which therapeutic activities to be administered are determined from the individual specific blood dose.

Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma.

PURPOSE: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure. METHODS AND MATERIALS: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOS_Eg software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation. RESULTS: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by (131)I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9). CONCLUSIONS: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors.

Biodistribution and radiation dosimetry of [11C]raclopride in healthy volunteers.

PURPOSE: This study reports on the whole-body biodistribution and radiation dosimetry of [11C]raclopride, a dopamine D2 receptor antagonist. METHODS: In three healthy male volunteers, whole-body scans were performed up to 2 h following i.v. injection of 320+/-65 MBq [11C]raclopride. Transmission scans (3 min per step, eight or nine steps according to the height of the subject) in 2D mode were used for subsequent attenuation correction of emission scans. Emission scans (1 min per step, eight or nine steps) were acquired over 2 h. Venous blood samples and urine were collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, lungs, kidneys and liver was fitted to a mono-exponential model, as an uptake phase followed by a mono-exponential washout, for urinary bladder to generate time-activity curves. Using the MIRD method, several source organs were considered in estimating residence time and mean effective radiation absorbed doses. RESULTS: Blood pressure and ECG findings remained unchanged after tracer injection. The analysed blood and urine pharmacological parameters did not change significantly after [(11)C]raclopride injection. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the gall-bladder, kidneys and liver. High activity was observed in the gall-bladder during the whole study. The kidneys, urinary bladder wall, liver and gall-bladder received the highest absorbed doses. The average effective dose of [11C]raclopride was estimated to be 6.7+/-0.4 microSv/MBq. CONCLUSION: The amount of [11C]raclopride required for adequate dopamine D2 receptor imaging results in an acceptable effective dose equivalent, permitting two or three repeated clinical PET imaging studies, with the injection of 222 MBq for each study.

Age-dependent variation of follicular size and expression of iodine transporters in human thyroid tissue.

UNLABELLED: The high sensitivity of the thyroid gland to the carcinogenic effects of radiation during childhood contrasts with the absence of demonstrable carcinogenic effects of radiation in adults. To better understand these age-related variations, we studied follicular morphometry, functional status, and proliferative activity in 31 thyroid glands removed from relatives of medullary thyroid carcinoma patients, with ages ranging from 3 to 39 y. METHODS: The mean follicular diameter (MFD) was estimated, and immunohistochemistry was performed with antibodies directed to molecules involved in iodide transport (Na(+)/I(-) symporter [NIS], pendrin, and apical iodide transporter), in organification (thyroperoxidase [TPO] and Duox), in cell cycle and growth (Ki-67, cyclin A and D1, and galectin-3), and in angiogenesis (vascular endothelial growth factor and nitric oxide synthase III [NOSIII]). RESULTS: Compared with older patients, patients who were < or =12 y old had a smaller MFD (P < 0.001) and more frequently positive NIS, pendrin, and Duox (P < 0.01). Proliferation rate as indicated by cyclin A expression was also higher in patients < 12 y (P < 0.01) but peaked at the time of puberty. Staining for NIS, pendrin, TPO, Duox, and NOSIII was stronger in thyroid glands with a smaller MFD (P < 0.001). On multiple tests adjusted for age and thyroid mass, TPO, Duox, and NOSIII remained significantly correlated to MFD (P < 0.001), whereas staining for NIS and pendrin did not. This finding suggests that NIS and pendrin expression is related mainly to the age of the patient. CONCLUSION: Smaller follicles with a higher expression of proteins involved in iodide metabolism were found in younger children. In cases of radioiodine contamination in children, the result will be a higher radioactive concentration and, hence, higher radiation doses. This event may induce the development of thyroid cancer under conditions of accelerated proliferation, as evidenced at puberty.

Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers.

UNLABELLED: This study reports on the biodistribution and radiation dosimetry of 2-(18)F-Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ((18)F-fluoro-A-85380), a promising radioligand for the imaging of central nicotinic acetylcholine receptors (nAChRs). METHODS: Whole-body scans were performed in 3 healthy male volunteers up to 2 h after intravenous injection of 137-238 MBq (18)F-fluoro-A-85380. Transmission scans (3 min per step, 8 or 9 steps according to the height of the subject) in 2-dimensional mode were used for subsequent correction of attenuation of emission scans. Emission scans (1 min per step) were acquired over 2 h. Venous blood samples were taken up to 2 h after injection of the radiotracer. Urine was freely collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, stomach, bladder, kidneys, and liver were fitted to a monoexponential model, as an uptake phase followed by a monoexponential washout, or to a biexponential model to generate time-activity curves. Using the MIRD method, ten source organs were considered in estimating radiation absorbed doses for organs of the body. RESULTS: Injection of (18)F-fluoro-A-85380 was clinically well tolerated and blood and urine pharmacologic parameters did not change significantly. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the bladder, kidneys, and liver. Slow uptake was seen in the brain. The liver received the highest absorbed dose. The average effective dose of (18)F-fluoro-A-85380 was estimated to be 0.0194 mSv/MBq. CONCLUSION: The amount of (18)F-fluoro-A-85380 required for adequate nAChR imaging results in an acceptable effective dose equivalent to the patient.

A hand-held imaging probe for radio-guided surgery: physical performance and preliminary clinical experience.

Improvements in the specificity of radiopharmaceutical compounds have been paralleled by an upsurge of interest in developing small detectors to assist surgeons in localizing tumour tissue during surgery. This study reports the main technical features and physical characteristics of a new hand-held gamma camera dedicated to accurate and real-time intra-operative imaging. First clinical experience is also reported. The POCI (Per-operative Compact Imager) camera consists of a head module composed of a high-resolution interchangeable lead collimator and a CsI(Na) crystal plate optically coupled to an intensified position-sensitive diode. The current prototype has a 40-mm diameter field of view, an outer diameter of 9.5 cm, a length of 9 cm and a weight of 1.2 kg. Overall detector imaging characteristics were evaluated by technetium-99m phantom measurements. Three patients with breast cancer previously scheduled to undergo sentinel lymph node detection were selected for the preliminary clinical experience. Preoperative images of the lymphatic basin obtained using the POCI camera were compared with conventional transcutaneous explorations using a non-imaging gamma probe. The full-width at half-maximum (FWHM) spatial resolution was investigated in both air and scattering medium; when the phantom was placed in contact with the collimator, the POCI camera exhibited a 3.2 mm FWHM. The corresponding sensitivity was 290 cps/MBq. The preliminary clinical results showed that POCI was able to predict the number and location of all SLNs. In one case, two deep radioactive nodes missed by the gamma probe were detected on the intra-operative images. This very initial experience demonstrates that the physical performance of the POCI camera is adequate for radio-guided surgery. These results are sufficiently encouraging to prompt further evaluation studies designed to determine the specific and optimal clinical role of intra-operative imaging devices.