Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer

Radioiodine therapy of thyroid cancer was the first and remains among the most successful radiopharmaceutical (RPT) treatments of cancer although its clinical use is based on imprecise dosimetry. The positron emitting radioiodine, (124)I, in combination with positron emission tomography (PET)/CT has made it possible to measure the spatial distribution of radioiodine in tumors and normal organs at high resolution and sensitivity. The CT component of PET/CT has made it simpler to match the activity distribution to the corresponding anatomy. These developments have facilitated patient-specific dosimetry (PSD), utilizing software packages such as three-dimensional radiobiological dosimetry (3D-RD), which can account for individual patient differences in pharmacokinetics and anatomy. We highlight specific examples of such calculations and discuss the potential impact of (124)I PET/CT on thyroid cancer therapy.     

Evaluation of renal function parameters with simultaneously administered 99mTc-DTPA and 131I-hippuran

The present study aimed at comparing two renal function tests using 99mTc-DTPA (diethylene triamine penta acetic acid) and 131I-labeled hippuran (o-hippuric acid). A mixture of 80 MBq 99mTc-DTPA and 7.4 MBq 131I-hippuran in a total volume of 1.5 ml or less was injected into an arm-vein. Both radiopharmaceuticals have identical initial distributions in the blood pool when injected in this manner. Seventy-two patients were studied with the present dual radionuclide technique. The following parameters were derived from the renogram: area under curve, uptake ratio, Tmax, decrease ratio, excretion ratio, and rate of decrease. The parameters for 99mTc-DTPA and 131I-hippuran were compared for various kidney groups. Generally the renographic parameters were well correlated. Apart from the systematic differences due to different modes of renal excretion, the curve patterns virtually agreed. The differences that were observed between the two tracers lacked clinical significance.     

124I PET/CT in the pretherapeutic staging of differentiated thyroid carcinoma: comparison with posttherapy 131I SPECT/CT

Purpose

To compare pretherapy ¹²⁴I PET/CT and posttherapy ¹³¹I SPECT/CT in the identification of pathological lesions and the staging of patients with differentiated thyroid carcinoma.

Methods

¹²⁴I SPECT with low-dose CT in addition to a standard whole-body scan was performed 5 days following ¹³¹I therapy with the administration of 1,110–7,728 MBq. Pretherapy ¹²⁴I PET/CT was done 24 h and 96 h after oral ingestion of 20–28 MBq, including a noncontrast high-dose CT scan. Scans were evaluated by two independent experienced nuclear physicians. In addition to the total number of lesions found, patient-based analyses and lesion-based analyses were performed to ascertain the discrepancies between the findings of the two scanning techniques, as well as to evaluate the clinical impact of the findings.

Results

A group of 20 consecutive patients were analysed. In the lesion-based analysis, a total of 62 foci were found with all modalities together. Of these, ¹²⁴I PET/CT found 57 (92 %), ¹³¹I SPECT/CT 50 (81 %) and planar imaging 39 (63 %). In the patient-based analysis, in 50 % of patients complete concordance between the findings of ¹²⁴I PET and ¹³¹I SPECT was seen, in 5 % complete discordance and in the remaining 45 % partial discordance, i.e. a focus or some foci seen with both modalities but another or others seen more or less with one or other modality. In 5 of the 20 patients (25 %), tumour stage was changed according to the findings of one of the modalities. In 60 % of these patients this was only with the findings of ¹²⁴I PET/CT.

Conclusion

This study showed that ¹²⁴I PET/CT is preferred over ¹³¹I imaging for staging differentiated thyroid carcinoma.     

Pre-therapeutic 124I PET(/CT) dosimetry confirms low average absorbed doses per administered 131I activity to the salivary glands in radioiodine therapy of differentiated thyroid cancer

Purpose  

Salivary gland impairment following high activity radioiodine therapy of differentiated thyroid cancer (DTC) is a severe side effect. Dosimetric calculations using planar gamma camera scintigraphy (GCS) with ¹³¹I and ultrasonography (US) provided evidence that the average organ dose per administered ¹³¹I activity (ODpA) is too low to account for observed radiation damages to the salivary glands. The objective of this work was to re-estimate the ODpA using ¹²⁴I PET(/CT) as a more reliable approach than ¹³¹I GCS/US.     

Quantitative imaging of 124I and 86Y with PET

The quantitative accuracy and image quality of positron emission tomography (PET) measurements with (124)I and (86)Y is affected by the prompt emission of gamma radiation and positrons in their decays, as well as the higher energy of the emitted positrons compared to those emitted by (18)F. PET scanners cannot distinguish between true coincidences, involving two 511-keV annihilation photons, and coincidences involving one annihilation photon and a prompt gamma, if the energy of this prompt gamma is within the energy window of the scanner. The current review deals with a number of aspects of the challenge this poses for quantitative PET imaging. First, the effect of prompt gamma coincidences on quantitative accuracy of PET images is discussed and a number of suggested corrections are described. Then, the effect of prompt gamma coincidences and the increased singles count rates due to gamma radiation on the count rate performance of PET is addressed, as well as possible improvements based on modification of the scanner's energy windows. Finally, the effect of positron energy on spatial resolution and recovery is assessed. The methods presented in this overview aim to overcome the challenges associated with the decay characteristics of (124)I and (86)Y. Careful application of the presented correction methods can allow for quantitatively accurate images with improved image contrast.     

Outpatient therapeutic 131I for thyroid cancer

OBJECTIVE: We retrospectively analyzed the safety, cost effectiveness, and patient acceptance of outpatient high-dose 131I treatment for thyroid cancer at our hospital since 1997, when the Nuclear Regulatory Commission began allowing high-dose outpatient therapy with radioiodine. METHODS: Forty-eight patients were treated as outpatients because their living conditions were acceptable and they were willing to comply with radiation safety guidelines. The homes of 3 patients were surveyed for contamination. The cost of outpatient treatment was compared with the cost of inpatient treatment. Patient acceptance was assessed by patient satisfaction surveys performed at the time of the posttherapy scan. RESULTS: No levels of contamination above regulatory levels were found in patients' homes. The cost of outpatient treatment was favorable. All surveyed patients were pleased with the procedure. CONCLUSION: If state and federal guidelines for releasing patients are followed, and if patients' living conditions are adequately assessed, outpatient treatment with high-dose 131I is safe and cost effective and improves patient satisfaction.     

Optimized 124I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer.

Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. METHODS: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20-40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (< or =5 Gy GBq(-1); n = 14), medium (between 5 and 10 Gy GBq(-1); n = 9), or high LDpAs (>10 Gy GBq(-1); n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lin's concordance correlation coefficient (rho c) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. RESULTS: The effective 124I half-life, linear activity-concentration rate (alpha), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a rho c value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. CONCLUSION: Lesion classification into LDpA groups was feasible using a single PET scan at approximately 24 h. Because of the highly variable kinetics, 1 additional measurement at approximately 96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.     

Prediction of absorbed dose to normal organs in thyroid cancer patients treated with 131I by use of 124I PET and 3-dimensional internal dosimetry software.

The objective of this work was to determine normal organ (131)I dosimetry in patients undergoing radioiodide therapy for thyroid cancer by use of serial scanning with (124)I PET. METHODS: A total of 26 patients who had papillary and follicular metastatic thyroid cancer and who were already enrolled in a Memorial Sloan-Kettering Cancer Center (131)I thyroid cancer protocol were selected for this study. Imaging before (131)I therapy consisted of multiple, whole-body (124)I PET studies over a period of 2-8 d, an (18)F-FDG PET scan and, for some, a diagnostic CT scan. With a set of in-house-developed software tools (3-dimensional internal dosimetry [3D-ID] and Multiple Image Analysis Utility [MIAU]), the following procedures were performed: all PET emission and transmission and CT image sets were aligned; half-life-corrected tomographic images of (131)I activity were integrated voxel by voxel to produce cumulated (131)I activity images; and the latter images were, in turn, convolved with a (131)I electron-photon point kernel to produce images of (131)I dose distribution. Cumulated activity values and calculated residence times obtained from our patient-specific dosimetry software (3D-ID) were used as inputs to OLINDA, and volume difference-adjusted comparisons were made between the mean dose estimates. RESULTS: With 3D-ID, dose volume histograms and mean doses were calculated for 14 organs, and results were expressed in Gy/GBq. The highest mean dose, 0.26 Gy/GBq, was seen in the right submandibular gland, whereas the lowest mean dose, 0.029 Gy/GBq, was seen in the brain. CONCLUSION: This is the first comprehensive study of normal organ dosimetry in patients by use of a quantitative tomographic imaging modality.     

Radiation Dose Assessment for I-131 Therapy of Thyroid Cancer Using I-124 PET Imaging

The goal for this work was to develop a method to determine the feasibility of estimating absorbed dose distribution of I-131 thyroid therapy using I-124 PET images of residual thyroid lesions with the dose constraint of 200 cGy to blood, that is a surrogate for bone marrow toxicity. A dose response study has been carried out on 3 patients with papillary thyroid carcinoma. Those patients were given 15-37 MBq of I-124 along with 74-185 MBq of I-131. PET imaging was performed 2-4 hour and then at 24 hour and either 48 hour, or 72 hour post-infusion. Lesion masses were computed from PET images using an adaptive thresholding technique. The definition of the boundary enabled determination of the iodine activity within the lesion. Time-activity curves were fitted to estimate the cumulated activity and therefore the absorbed dose per MBq administered. Daily blood and total body counts were performed on the patients using a multichannel analyzer with windows set for both I-131 (364 keV) and I-124 (511 keV). Cross-talk corrections from one isotope into the alternate window was determined using a standard of each respective isotope. At maximum-tolerated-activity (MTA) that delivers 200 cGy radiation dose to the blood, the dose to lesions from I-131 varied from 0.04 to 2.44 cGy/MBq (1.57-90.48 rads/mCi) with effective half-lives for I-124 ranging from 0.58 to 1.86 days. The three-dimensional absorbed dose distribution in the thyroid lesions was calculated by convolving the activity values with an I-131 point-source kernel using a Fast Hartley Transform. The calculated mean absorbed dose distribution was displayed as isodose lines on PET images that can be used to refine the amount of administered activity. PET with I-124 may improve the absorbed dose estimates from radioiodine therapy with I-131 in the treatment of thyroid cancer. The capability of estimating I-131 mean absorbed dose distributions from serial I-124 PET images can lead to patient-specific treatment planning for thyroid therapy.     

PET quantitation and imaging of the non-pure positron-emitting iodine isotope 124I.

A series of PET studies using phantoms is presented to characterize the imaging and quantitative performance of the positron-emitting iodine isotope 124I. Measurements were performed on the 2D-PET scanner GE 4096+ as well as on the Siemens PET scanner HRR+ operated in both 2D and 3D modes. No specific correction was applied for the gamma-rays emitted together with the positrons. As compared to 18F, in studies with 124I there is a small loss of image resolution and contrast, and an increase in background. The quantitative results varied between different scanners and various acquisition as well as reconstruction modes, with an average relative difference of -6 +/- 13% (mean+/-SD) in respect of the phantom radioactivity as measured with gamma-ray spectroscopy. We conclude that quantitation of a radiopharmaceutical labelled with 124I is feasible and may be improved by the development of specific corrections.     

NCL-6-124I: a PET agent for the adrenal

The radiopharmaceutical 6β-[¹²⁴I]iodomethyl-19-norcholest-5(10)-en-3β-ol (NCL-6-¹²⁴I) was synthesized. The product was less sensitive to autoradiolytic decomposition in chloroform, than when stored as an injectable solution at 5°C.     

Health effects of therapeutic use of 131I in hyperthyroidism.

Since 1942, therapy with radioiodine (Na131I) has gained a major role in the treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves' disease or toxic multinodular goiter. The very large series of patients treated so far offer the opportunity for an assessment of both benign and malignant side effects. Hyperthyroidism is sometimes observed after radioiodine therapy due to radiation induced thyroid hormone or by an immunological mechanism. Despite the numerous attempts to design dosage schedules aiming at euthyroidism, hypothyroidism occurs in the majority of patients throughout life. Transient hypothyroidism may be observed within the first year after therapy and is caused by an immunological mechanism. Radioiodine therapy in Graves' disease may induce or worsen ophthalmopathy, which can be prevented by steroids effectively. Hypoparathyroidism and hyperparathyroidism have been reported after radioiodine therapy but probably do not exceed the normal incidence. Sialitis is commonly observed but mostly in patients treated with radioiodine for thyroid cancer. There are no indications for induction of genetic abnormalities after radioiodine therapy although no definite conclusion can be reached. Much attention has been paid to malignant disease. In very large series, no effects of radioiodine therapy on survival have been observed. Some studies report an increased relative risk for certain types of cancer (notably thyroid cancer, stomach cancer, bladder and kidney cancer or hematological malignancies). However, these observations were not confirmed by other large studies, so that no definite conclusion with respect to risk for certain types of malignant disease can be drawn. However, radioiodine therapy for benign thyroid disorders has generally been considered safe and without major side effects, hypothyroidism being the most frequent one.     

Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan.

The management of metastatic thyroid carcinoma patients with a negative 131I scan presents considerable problems. Fifty-four athyrotic papillary thyroid carcinoma patients whose 1311 whole-body scans were negative underwent 18F-fluorodeoxyglucose (FDG) PET; the purpose was to determine whether this procedure could localize metastatic sites. We also assessed its usefulness in the management of these patients. METHODS: Whole-body emission scan was performed 60 min after the injection of 370-555 MBq 18F-FDG, and additional regional attenuation-corrected scans were obtained. Metastasis was pathologically confirmed in 12 patients and was confirmed in other patients by overall clinical evaluation of the findings of other imaging studies and of the subsequent clinical course. RESULTS: In 33 patients, tumor had metastasized, whereas 21 patients were in remission. FDG PET revealed metastases in 31 patients (sensitivity 93.9%), whereas thyroglobulin levels were elevated in 18 patients (sensitivity 54.5%). FDG PET was positive in 14 of 15 metastatic cancer patients with normal thyroglobulin levels. In 20 of 21 patients in remission, FDG PET was negative (specificity 95.2%), whereas thyroglobulin levels were normal in 16 patients (specificity 76.1%). The sensitivity and specificity of FDG PET were significantly higher than those of serum thyroglobulin. In patients with negative 1311 scans, FDG PET detected cervical lymph node metastasis in 87.9%, lung metastasis in 27.3%, mediastinal metastasis in 33.3% and bone metastasis in 9.1%. In contrast, among 117 patients with 131I scan-positive functional metastases, 131I scan detected cervical lymph node metastasis in 61.5%, lung metastasis in 56.4%, mediastinal metastasis in 22.2% and bone metastasis in 16.2%. In all 5 patients in whom thyroglobulin was false-negative with negative antithyroglobulin antibody, PET showed increased 18F-FDG uptake in cervical lymph nodes, mediastinal lymph nodes, or both. Among patients with increased 18F-FDG uptake only in the cervical lymph nodes, the nodes were dissected in 11. Metastasis was confirmed in all, even in normal-sized lymph nodes. CONCLUSION: FDG PET scan localized metastatic sites in 131I scan-negative thyroid carcinoma patients with high accuracy. In particular, it was superior to 131I whole-body scan and serum thyroglobulin measurement for detecting metastases to cervical lymph nodes. FDG PET was helpful for determining the surgical management of these patients.     

Radiological protection guidance for radioactive patients--new data for therapeutic 131I

Patients leaving hospital after 131I treatment for thyrotoxicosis face restrictions on their contact with other members of the public. These restrictions depend on the level of residual body radioactivity which for practical purposes can be taken to be almost entirely in the thyroid gland. This study provides an appropriate data base from which to draw advice to patients consistent with current radiological protection requirements in terms of the duration of these restrictions. Thyroidal retention of 131I was measured in 77 thyrotoxic patients over a period of 1-50 days after a first therapeutic administration of the radionuclide. Mean 131I activity in the gland (+/- S.D.) at 1 day was 56.1 +/- 11.1% of the administered dose activity and thereafter retention followed a single exponential decay pattern with a mean effective half-life (+/- S.E.M.) of 6.35 +/- 0.14 days. In patients who required further 131I therapy, there was evidence that retention could be markedly reduced if there was virtual ablation of thyroid tissue. It is proposed that these retention data can be used to determine body radioactivity at any interval after the administration of 131I for treatment of thyrotoxicosis, thus obviating the need for serial measurements in every individual patient.     

124I PET/CT在分化型甲状腺癌诊治中的应用

近年来,124I PET/CT在DTC诊治中的应用引起了临床工作者越来越广泛的关注.结合CT精确的解剖学信息和PET高特异的功能学信息,124I PET/CT可准确定位摄碘性病灶,探测非摄碘性病灶,从而更好地对DTC进行分期.此外,依赖其准确的剂量学评价结果,124I PET/CT剂量学评价可辅助制定DTC患者的治疗方案.笔者概述了124I PET/CT在DTC诊治中的应用.     

Optimization of 124I production via 124Te(p,n)124I reaction.

(124)I was produced, via (124)Te(p,n)(124)I reaction, in greater than 3.7GBq (100 mCi, EOB) amount by bombarding (124)TeO(2) targets at 24 microA current for about 8h. This was achieved by keeping the target at 37 degrees relative to the beam during irradiation, by sweeping the beam across the target and by keeping the incident energy of the proton at 14.1MeV. The time-averaged yield of our 8h run was 21.1 MBq/microAh (0.57 mCi/microAh), which was 90% of the theoretical yield calculated using thick target yield data obtained from the reported excitation function for the reaction. At the end of bombardment, the level of (125)I and (126)I impurities, co-produced with (124)I, were 0.03% and 0.007%, respectively.     

A new binary compound for the production of 124I via the 124Te(p,n)124I reaction.

The binary compound, aluminum telluride (Al(2)Te(3)), was investigated as a target material for the production of (124)I by way of the (124)Te(p,n)(124)I reaction on a low-energy cyclotron. The high melting point and formation of a glassy matrix upon heating provided a stable target material at irradiations up to 20 microA of 11 MeV protons. The 87% tellurium mass fraction and 95% iodine separation yield led to significantly higher quantities of iodine compared to traditional TeO(2)/6%Al(2)O(3) admixtures. Radiochemical analysis of distilled samples using ion chromatography showed that the product remained in the iodide form while supported in weak buffer solutions. Stable Te impurities in the radioiodine product were less than 0.5 microg following purification by ion exchange chromatography. Average thick target yields of 229+/-18 microCi/microAh were achieved, and typical production runs at 18 microA for three hours yielded 12 mCi at the end-of-bombardment. Total losses of the target material after each irradiation and distillation cycle were approximately 2%.