Thyroid remnant ablation using 1,110?MBq of I-131 after total thyroidectomy: regulatory considerations on release of patients after unsealed radioiodine therapy

Objectives

This study was undertaken to measure the radiation exposure level of caregivers following outpatient NaI (I-131) 1,110?MBq therapy for remnant thyroid ablation after total thyroidectomy in patients with differentiated thyroid cancer, and to evaluate the influence of activities of daily living on radiation exposure level, with the goal of proposing an optimum method of I-131 therapy.

Methods

The study included 37 patients with differentiated thyroid cancer, who had undergone total thyroidectomy and received outpatient based remnant thyroid ablation using NaI (I-131) 1,110?MBq, who were satisfying the following requirements: (1) patients who have no evidence of distant metastases, (2) whose living environments were appropriate for outpatient I-131 (1,110?MBq) therapy, and (3) patients who gave written informed consent. The dose rate at a distance of 1?m from the body surface of the patient at the moment of release was measured using survey meters of the GM type or ionization chamber type. The dose level for the caregiver was measured with a personal dosimeter in all cases.

Results

The dose rate at a distance of 1?m from the patient??s body surface 1?h after I-131 administration was in the range of 29?C115???Sv/h (mean 63.8???Sv/h). The 7-day cumulative effective dose of caregivers was 0.11?±?0.08?mSv, on an average, in 34 dosimeters. In 31 of 34 dosimeters, cumulative effective dose of caregivers was below 0.2?mSv. Dose levels exceeding 0.2?mSv were recorded in 3 cases (0.21, 0.35 and 0.43?mSv in one case each). These results suggest that the exposure level of family members (caregiver and others) was minimal and is lower than the radiation levels affecting human environments.

Conclusion

Outpatient-based remnant thyroid ablation with I-131 (1,110?MBq) performed after total thyroidectomy in patients with differentiated thyroid cancer is safe if applied in accordance with the appropriate supervision and guidance by experts with certain qualifications.     

Adjuvant thyroid remnant ablation in patients with differentiated thyroid carcinoma confined to the thyroid: a comparison of ablation success with different activities of radioiodine (I-131)

Objective

To assess efficiency of various I-131 activities on thyroid remnant ablation in thyroid cancer patients. The significance of patients?? characteristics, pathologic features and levels of Tg were analyzed.

Patients and methods

This study included 259 consecutive differentiated thyroid cancer patients, with disease confined to the thyroid, treated with I-131 after total thyroidectomy. Patients were divided into the three groups: 80 patients receiving low [1110?C1850?MBq (30?C50?mCi)], 121 intermediate [2775?MBq (75?mCi)] and 58 high [3700?MBq (100?mCi)] postoperative I-131 activities. Six to eight months after the application of radioiodine, measurements of TSH, Tg, anti-Tg antibodies (in hypothyroid state) together with ultrasound exam and whole-body scintigraphy were performed.

Results

The ablation was significantly more effective (after the first application) in patients receiving 100?mCi of I-131??89.7?% than in patients receiving lower activities (P?=?0.016). There was no significant difference in ablation rate between the 30?C50?mCi (77.5?%) and 75?mCi (70.2?%) groups. In the group receiving 30?C50?mCi, patients with solitary tumors had significantly higher ablation rate (P?=?0.038). In patients receiving 75?mCi ablation rates were higher among older patients (P?=?0.005), with infiltration of the single lobe (P?=?0.005), and with solitary tumor (P?=?0.012). The rates of successful ablation after the second application of I-131 (after 12?C16?months) amounted to 96, 97 and 96?% in the 30?C50, 75 and 100?mCi groups, respectively. The activity of I-131 and age were independent factors for thyroid ablation failure after the first application of I-131 (model of binary logistic regression).

Conclusion

The results of remnant ablation were satisfactory with all activities applied. Although after the first application of I-131 the activity of 100?mCi is significantly more effective in thyroid ablation than the administration of 30?C50?mCi and 75?mCi, the ablation rates between all the three groups are similar (almost equal) after the second application. Thus, the activity to be administered may depend on patients?? characteristics and a detailed consideration of the merits and demerits of each I-131 activity.     

Biodistribution and radiation dosimetry in healthy volunteers of a novel tumour-specific probe for PET/CT imaging: BAY 85-8050

Purpose

Novel tracers for the diagnosis of malignant disease with PET and PET/CT are being developed as the most commonly used ¹⁸F deoxyglucose (FDG) tracer shows certain limitations. Employing radioactively labelled glutamate derivatives for specific imaging of the truncated citrate cycle potentially allows more specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a glutamate derivative, was calculated and the effective dose (ED) was compared with that of FDG.

Methods

Five healthy volunteers were included in the study. Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at 120 and at 240 min after injection of 305.0?±?17.6 MBq of BAY 85-8050. Organs with moderate to high uptake at any of the imaging time points were used as source organs. Total activity in each organ at each time point was measured. Time–activity curves (TAC) were determined for the whole body and all source organs. The resulting TACs were fitted to exponential equations and accumulated activities were determined. OLINDA/EXM software was used to calculate individual organ doses and the whole-body ED from the acquired data.

Results

Uptake of the tracer was highest in the kidneys due to renal excretion of the tracer, followed by the pancreas, heart wall and osteogenic cells. The mean organ doses were: kidneys 38.4?±?11.2 μSv/MBq, pancreas 23.2?±?3.8 μSv/MBq, heart wall 17.4?±?4.1 μSv/MBq, and osteogenic cells 13.6?±?3.5 μSv/MBq. The calculated ED was 8.9?±?1.5 μSv/MBq.

Conclusion

Based on the distribution and dose estimates, the calculated radiation dose of BAY 85-8050 is 2.67?±?0.45 mSv at a patient dose of 300 MBq, which compares favourably with the radiation dose of FDG (5.7 mSv).     

Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide

Purpose

The biokinetics and dosimetry of ¹¹¹In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and ¹¹¹In-DTPA-octreotide (Octreoscan?, OCTREO) were compared in the same patients.

Methods

Seventeen patients (10 men, 7 women; mean age 60?years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior–posterior scans were recorded 0.5 (100?% reference scan), 4, 24 and 48?h (17 patients) and 120?h (5 patients) after injection. In 16 patients the OCTREO scan (178?±?15?MBq) was performed 16?±?5?days before the NOCATE scan (108?±?14?MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5?min to 48?h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM.

Results

Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p?<?0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood T _1/2β for NOCATE was longer (19 vs. 6?h). As a result, the effective dose of NOCATE (105?μSv/MBq) exceeded that of OCTREO (52?μSv/MBq), and the latter result was similar to the ICRP 106 value of 54?μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5?% of NOCATE and OCTREO attached to globular blood components.

Conclusion

NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.     

Radiation dosimetry and first therapy results with a 124I/131I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy

Introduction

Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[¹²⁴I]iodophenyl)ureido)pentyl)ureido)pentanedioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of ¹³¹I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of ¹³¹I-MIP-1095.

Methods

Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of ¹²⁴I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of ¹³¹I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA.

Results

I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq, liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or moderate reduction in pain. Hematological toxicities were mild. Of men treated, 25 % had a transient slight to moderate dry mouth. No adverse effects on renal function were observed.

Conclusion

Based on the biodistribution and dose calculations of the PSMA-targeted small molecule ¹²⁴I-MIP-1095 therapy with the authentic analog ¹³¹I-MIP-1095 enables a targeted tumor therapy with unprecedented doses delivered to the tumor lesions. Involved lymph node and bone metastases were exposed to estimated absorbed doses upwards of 300 Gy.     

Usefulness of partial volume effect-corrected F-18 FDG PET/CT for predicting I-131 accumulation in the metastatic lymph nodes of patients with thyroid carcinoma

Purpose

The purpose of this study was to evaluate the clinical usefulness of partial volume effect (PVE)-corrected F-18 FDG PET/CT for predicting I-131 accumulation in metastatic lymph nodes (mLNs) during I-131 therapy for papillary thyroid carcinoma (PTC).

Methods

Sixty-five mLNs in 31 PTC patients who underwent F-18 FDG PET/CT in an initial radioiodine therapy (RIT) were retrospectively evaluated. Of these, 25 mLNs were I-131-positive and 40 were I-131-negative. SUVmax and SUVmax with PVE correction (cSUVmax) were measured for each mLN, where PVE correction was performed utilizing a simple table lookup correction method. Then, SUVmax/cSUVmax was compared between I-131-positive and I-131-negative mLNs, including the analyses for the mLNs with small-sized (<1 cm) and weak FDG accumulation (SUVmax <3.5). The predictability for I-131 accumulation with SUVmax/cSUVmax was also compared.

Results

For all 65 mLNs, SUVmax/cSUVmax was significantly higher in I-131-negative than I-131-positive mLNs (p < 0.0001). Only in cSUVmax, I-131-negative mLNs were significantly higher than I-131-positive, in terms of the 30 small-sized mLNs (p = 0.0001) and 14 mLNs with weak FDG uptake (p = 0.007). The highest accuracy in predictability for I-131 accumulation was significantly better with cSUVmax (92 %) than SUVmax (62 %) (p < 0.0001).

Conclusion

PVE-corrected F-18 FDG PET/CT is a valuable predictor of I-131 accumulation in mLNs during RIT.     

11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: radiometabolism,plasma pharmacokinetics,whole-body distribution and radiation dosimetry in healthy men

Purpose

¹¹C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl]-4-(3-methoxy-methylpyridin-2-yl)-piperazine (¹¹C-ORM-13070) is a novel PET tracer for imaging of α_2C-adrenoceptors in the human brain. Brain α_2C-adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer’s disease. To validate the use of ¹¹C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose.

Methods

Radiometabolism was studied in a test–retest setting in six healthy men. After intravenous injection of ¹¹C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time–activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of ¹¹C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling.

Results

Two radioactive metabolites of ¹¹C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged ¹¹C-ORM-13070 decreased from 81?±?4 % of total radioactivity at 4 min after tracer injection to 23?±?4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged ¹¹C-ORM-13070 in arterial plasma were 0.0117?±?0.0056 min^?1 and 73.6?±?35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 – 4.2 μSv/MBq.

Conclusion

¹¹C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of ¹¹C-ORM-13070 was in the same range as that of other ¹¹C-labelled brain receptor tracers. An injection of 500 MBq of ¹¹C-ORM-13070 would expose a subject to 2.0 mSv of radiation. This supports the use of ¹¹C-ORM-13070 in repeated PET scans, for example, in receptor occupancy trials with novel drug candidates.     

Human biodistribution and dosimetry of 18F-JNJ42259152, a radioligand for phosphodiesterase 10A imaging

Purpose

Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP-hydrolysing enzyme with a central role in striatal signalling and implicated in neuropsychiatric disorders such as Huntington’s disease, Parkinson’s disease, schizophrenia and addiction. We have developed a novel PDE10A PET ligand, ¹⁸F-JNJ42259152, and describe here its human dynamic biodistribution, safety and dosimetry.

Methods

Six male subjects (age range 23–67 years) underwent ten dynamic whole-body PET/CT scans over 6 h after bolus injection of 175.5?±?9.4 MBq ¹⁸F-JNJ42259152. Source organs were delineated on PET/CT and individual organ doses and effective dose were determined using the OLINDA software.

Results

F-JNJ42259152 was readily taken up by the brain and showed exclusive retention in the brain, especially in the striatum with good washout starting after 20 min. The tracer was cleared through both the hepatobiliary and the urinary routes. No defluorination was observed. Organ absorbed doses were largest for the gallbladder (239 μSv/MBq) and upper large intestine (138 μSv/MBq). The mean effective dose was 24.9?±?4.1 μSv/MBq. No adverse events were encountered.

Conclusion

In humans, ¹⁸F-JNJ42259152 has an appropriate distribution, brain kinetics and safety. The estimated effective dose was within WHO class IIb with low interindividual variability. Therefore, the tracer is suitable for further kinetic evaluation in humans.     

Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium

Background and aim

Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium.

Methods

A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus.

Results

Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p?<?0.05) and of WBS negativity (97.7% vs. 81.8%, p?<?0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p?<?0.001).

Conclusion

rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.     

Very low-activity stress/high-activity rest, single-day myocardial perfusion SPECT with a conventional sodium iodide camera and wide beam reconstruction processing

Background

A stress (S)/rest (R) 1-day Tc-99m sestamibi protocol is logistically advantageous and facilitates stress-only imaging. However, with conventional 370?MBq (10?mCi) S activity and subsequent 1,110-1,295?MBq (30-35?mCi) R activity there is a risk of S-to-R ??shine-through?? and underestimation of defect reversibility. New software methods cope with lower counting statistics and should allow for both a reduced S activity and also less likelihood of S-to-R ??shine-through.??

Methods

102 prospective patients [49 men, 53 women; mean weight 178?±?41 lbs (range 98-265?lbs); chest 41.5???±?4.0?? (range 32??-52??)] received 192.4?+?18.5?MBq (5.2?±?0.5?mCi) Tc-99m sestamibi S (25 exercise, 77 regadenoson) activity followed in 30-40?minutes by ??full-time?? (12?minutes) two-headed NaI camera S SPECT. Immediately thereafter, a 16-minute S SPECT acquisition was also performed in 37/102 patients. Then at 60-80?minute post-S all patients received 1328.3?+?129.5?MBq (35.9?±?3.5?mCi) Tc-99m sestamibi, and ??half-time?? (7.5?minutes) R SPECT was acquired. All tomograms were processed with wide beam reconstruction (WBR, UltraSPECT Ltd.) software. A time-adjusted R/S myocardial count density ratio (MCDR) was calculated using automated software. S SPECT quality was visually graded (poor, fair, good, excellent) based upon myocardial definition, cavity contrast, RV visualization, and noise. For comparison, the S/R MCDR was calculated in 581 consecutive patients undergoing a conventional 370?MBq R/1110?MBq S (10?mCi R/30?mCi S) protocol.

Results

S SPECT was normal in 44 patients (43%). Image quality was good-excellent in 93 (91%) patients with 12-minute S SPECT. Also in 37 (98%) patients with 16-minute S SPECT, quality was good-excellent. In patients with >42?? chests 12-minute S SPECT quality worsened with increasing chest circumference, manifested by myocardial ??blurring.?? Image quality improved by ??1 grade in the 12/37 patients (32%) also undergoing 16-minute S SPECT. The time- and decay-corrected 12-minute mean R/S MCDR was 5.78, a ratio adequate to minimize S-to-R shine-through, as verified in phantom experiments, and significantly better than a 3.79 S/R ratio achieved in the 581 patients undergoing a conventional R/S protocol.

Conclusions

An approximately 185?MBq (5?mCi S) Tc-99m SPECT processed with WBR provides adequate image quality. For larger patients prolonging image acquisition to 16?minutes is beneficial. For patients with normal S SPECT, a S-only protocol is feasible, affording them a very low (approximately 1.4?mSv) radiation dose. If subsequent R SPECT is necessary, it can be performed with approximately 1,332?MBq (36?mCi) with minimal S-R ??shine-through.??     

Application of a medium-energy collimator for I-131 imaging after ablation treatment of differentiated thyroid cancer

Purpose

High-energy (HE) collimators are usually applied for I-131 imaging after ablation treatment of differentiated thyroid cancer (DTC). However, purchase of HE collimators has been avoided in many nuclear medicine departments because the HE collimators are more expensive than other collimators. In this study, we compared the I-131 imaging using HE- and medium-energy (ME) collimators, which is more versatile than HE collimators.

Materials and methods

To simulate DTC patients with extra-thyroid beds, a phantom of acrylic containers containing I-131 was used. To simulate patients with thyroid beds, four phantoms representing extra-thyroid beds were arranged around the phantom representing normal thyroid tissues. Patients administered 1.11 or 3.70 GBq NaI-131 were also evaluated. Whole-body imaging and SPECT imaging of the phantoms and patients performed using HE-general-purpose (HEGP) and ME-low-penetration (MELP) collimators, and full-width at half maximum (FWHM) and percent coefficient of variation (%CV) were measured.

Results

In the extra-thyroid beds, FWHM and %CV with MELP were negligibly different from those with HEGP in whole-body imaging. Although FWHM with MELP was a little different from that with HEGP in SPECT imaging, %CV with MELP was significantly higher than that with HEGP. In the thyroid beds, only an extra-thyroid bed including higher radioactivity was identified in whole-body imaging with both collimators. Although SPECT images with MELP could not clarify extra-thyroid beds with low radioactivity, HEGP could identify them. In patients, although some whole-body images with MELP could not detect extra-thyroid beds, whole-body imaging with HEGP and SPECT imaging with both collimators could detect them.

Conclusions

Although HEGP is the best collimator for I-131 imaging, MELP is applicable for not only whole-body imaging but also SPECT imaging.     

Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid

Purpose

Radioimmunotherapy (RIT) using ¹³¹I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of ¹³¹I-3F8 and to identify limiting factors that may impact therapeutic ratio.

Methods

Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[C_IAR]), (2) that of the unbound antibody AUC[C_IA], and (3) their therapeutic ratio (AUC[C_IAR]/AUC[C_IA]).

Results

Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R?=?0.95?±?0.03). Correlations were substantially better when compared to the one-compartment model (R?=?0.92?±?0.11 versus 0.77?±?0.21, p?=?0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of ¹³¹I-3F8 from 10% to 90% increased both (AUC[C_IAR]) and therapeutic ratio ([AUC[C_IAR]/AUC[C_IA]] by 7.4 fold, (2) When extrapolated to the clinical setting, the model predicted that if ¹³¹I-3F8 could be split into 4 doses of 1.4 mg each and given at ≥24 hours apart, an antibody affinity of K_D of 4?×?10^-9 at 50% immunoreactivity were adequate in order to deliver ≥100 Gy to tumor cells while keeping normal CSF exposure to <10 Gy.

Conclusions

This model predicted that immunoreactivity, affinity and optimal scheduling of antibody injections were crucial in improving therapeutic index.

     

Carcinoma of the breast wire localisation post nuclear medicine sentinel lymph node imaging. Are radiologists receiving a significant dose?

Objective

To assess the radiation dose received by the radiologist when performing wire localisation for axillary radio-isotope sentinel node imaging-guided biopsy in patients with impalpable breast cancers treated with breast-preserving excision. When wire placement follows radio-isotope sentinel node imaging (RSNI) the radiologist is exposed to a radiation risk that has never been previously assessed.

Methods

Radiation doses to radiologists performing ultrasound-guided localisation following nuclear medicine sentinel node imaging were measured for procedures on the day of surgery (20 MBq) and also on the day before surgery (40 MBq). These measurements were compared with theoretically calculated doses.

Results

Twelve patients showed comparable results between measurements and estimated doses. The mean measured dose was 1.8 μSv (estimated 1.8 μSv) for same-day and 4.8 μSv (estimated 3.4 μSv) for next-day surgery cases. At worst, radiologists who perform 36 wire localisations per year immediately following RSNI receive a radiation dose of 0.17 mSv.

Conclusions

This study highlights the need to inform radiologists of the relative risk when performing pre-surgical localisation after RSNI. This risk should be justified locally in accordance with the total dose received by the localising radiologist. Particular consideration should be given to pregnant staff and the possibility of performing wire localisations before radio-isotope injection.     

Value of SPECT/CT in Diagnostic I-131 MIBG Scintigraphy in Patients with Neuroblastoma

Purpose

Diagnostic I-131 MIBG scintigraphy is an important imaging modality for evaluation of patients with neuroblastoma (NB) especially in centers where I-123 MIBG is not available. Single photon emission computed tomography/computed tomography (SPECT/CT) could potentially improve lesion detection over planar scintigraphy, but studies regarding its usefulness as an add-on to diagnostic I-131 MIBG scintigraphy are limited. This study aimed to determine the usefulness and factors related to usefulness of SPECT/CT in diagnostic I-131 MIBG scintigraphy in NB patients.

Methods

Usefulness of SPECT/CT for lesion detection, lesion localization, resolving suspicious findings, and clarifying the nature of lesions on anatomical imaging were retrospectively reviewed in 86 diagnostic planar I-131 MIBG scintigrams with add-on SPECT/CT.

Results

SPECT/CT detected additional lesions in 23.2%(20/86), helped localize lesions in 21.1%(8/38), resolved suspicious findings in 85.7%(6/7), determined functional status of lesions on anatomical imaging in 94.4%(17/18), and changed diagnosis from a negative to a positive study in 19.5%(8/41). Independent predictors of SPECT/CT being useful included presence of suspicious findings on planar imaging (OR 99.08; 95% C.I. 6.99–1404.41; p?=?0.001), positive findings on planar imaging (OR 4.61; 95% C.I. 1.05, 20.28; p?<?0.001), and presence of structural lesions on anatomical imaging (OR 32.54; 95% C.I. 5.37–196.96; p?<?0.001).

Conclusion

SPECT/CT is a useful add-on to diagnostic planar I-131 MIBG scintigraphy. Predictors of usefulness of SPECT/CT include suspicious or positive findings on planar scintigraphy and the presence of structural lesions on anatomical imaging.

     

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

Objectives

Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of <1?mm, but few studies have focused on the evaluation of intratumoral heterogeneity. We investigated the optimal conditions related to high resolution imaging of heterogeneous tumor interiors using a small animal SPECT scanner.

Methods

The conditions related to SPECT/CT visualization of heterogeneous tumor interiors were investigated using phantoms with ¹¹¹In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice.

Results

Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30?min, better image quality was obtained with pinhole apertures diameter of 1.4?mm than of 1.0?mm. The obtained best spatial resolution was 1.3?mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0?mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2?C0.5?MBq/mL. Liposomes containing ¹¹¹In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous ¹¹¹In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2?MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes.

Conclusion

Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.     

Predictive factors for the outcomes of initial I-131 low-dose ablation therapy to Japanese patients with differentiated thyroid cancer

Objective

To identify prognostic factors associated with a low-iodine diet (LID) and the amount of remnant thyroid tissue in Japanese patients with differentiated thyroid cancer (DTC) who received initial I-131 remnant ablation (RAI) using a fixed low dose of I-131 (1110 MBq).

Patients and methods

In this prospective study, we enrolled 45 patients. Patients were classified into a self-managed LID group and a strict LID group. We measured the urinary iodine concentration on the day of RAI after patients consumed LID for 2 weeks. Thyroid-stimulating hormone-induced thyroglobulin (Tg) levels and I-131 uptake by the remnant thyroid tissue were also evaluated. A response-evaluation whole-body scan (WBS) was performed 6–8 months after RAI to determine the outcome of the therapy.

Results

Post-LID urinary iodine levels of the strict LID group tended to be lower than those of the self-managed LID group. Twenty-five cases (56%) showed absence of uptake, whereas 20 cases (44%) showed residual uptake on the response-evaluation WBS. There were no significant differences between “absence” and “residual” groups in urinary iodine concentrations and Tg levels (p?=?0.253 and p?=?0.234, respectively). However, significant differences were observed in I-131 uptake by the thyroid bed (p?=?0.035).

Conclusions

For patients following the current Japanese method of a 2-week LID, the urinary iodine concentration was not a predictive factor for the successful outcome of RAI. In contrast, low I-131 uptake by the thyroid bed, revealed by the scintigram after RAI, may serve as a favorable predictive factor.

     

Toxicity of upfront 131I-metaiodobenzylguanidine (131I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis

Purpose

In the treatment of patients with high-risk neuroblastoma, different doses of ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) are administered at different time points during treatment. Toxicity, mainly haematological (thrombocytopenia), from ¹³¹I-MIBG therapy is known to occur in extensively chemotherapy pretreated neuroblastoma patients. Up to now, acute toxicity from ¹³¹I-MIBG as initial treatment has never been studied in a large cohort. The aim of this retrospective study was to document acute toxicity related to upfront ¹³¹I-MIBG.

Methods

All neuroblastoma patients (stages 1–4 and 4S) treated upfront with ¹³¹I-MIBG at the Emma Children’s Hospital, Academic Medical Centre (1992 – 2008) were included in this retrospective analysis. The acute toxicity (during therapy) and short-term toxicity (1st month following therapy) of the first two ¹³¹I-MIBG therapies were studied.

Results

Of 66 patients (34 boys, 32 girls; median age 2.2 years, range 0.1 – 9.4 years), 49 had stage 4 disease, 5 stage 4S, 6 stage 3, 1 stage 2 and 5 stage 1. The median first dose was 441 MBq/kg (range 157 – 804 MBq/kg). The median second dose was 328 MBq/kg (range 113 – 727 MBq/kg). The most frequently observed symptoms were nausea and vomiting (21 %, maximum grade II). The main toxicity was grade IV haematological, occurring only in stage 4 patients, after the first and second ¹³¹I-MIBG therapies: anaemia (5 % and 4 %, respectively), leucocytopenia (3 % and 4 %) and thrombocytopenia (2 % and 4 %). No stem cell rescue was needed.

Conclusion

The main acute toxicity observed was haematological followed by nausea and vomiting. One patient developed posterior reversible encephalopathy syndrome during ¹³¹I-MIBG therapy, possibly related to ¹³¹I-MIBG. We consider ¹³¹I-MIBG therapy to be a safe treatment modality.     

Impact of iterative reconstruction on CT coronary calcium quantification

Objectives

We evaluated the influence of sinogram-affirmed iterative reconstruction (SAFIRE) on the coronary artery calcium (CAC) score by computed tomography (CT).

Materials and methods

Seventy patients underwent CAC imaging by 128-slice dual-source CT. CAC volume, mass and Agatston score were calculated from images reconstructed by filtered back projection (FBP) without and with incremental degrees of the SAFIRE algorithm (10-50 %). We used the repeated measuring test and the Steel-Dwass test for multiple comparisons of values and the difference ratio among different SAFIRE groups using the FBP as reference.

Results

The median Agatston score (range) decreased with incremental SAFIRE degrees: 163 (0.1???3,393.3), 158.4 (0.3???3,079.3), 137.7 (0.1???2,978.0), 120.6 (0???2,783.6), 102.6 (0???2,468.4) and 84.1 (0???2,186.9) for 0 % (FBP), 10 %, 20 %, 30 %, 40 % and 50 % SAFIRE, respectively (P?<?0.05). In comparison with FBP, CAC volume (from 8.1 % to 47.7 %), CAC mass (from 5.3 % to 44.7 %) and CAC Agatston score (from 7.3 % to 48.4 %) all decreased with increasing SAFIRE from 10 % to 50 %, respectively (P?<?0.05). High-grade SAFIRE resulted in the disappearance of detectable calcium in three cases with low calcium burden.

Conclusion

SAFIRE noise reduction techniques significantly affected the CAC, which potentially alters perceived cardiovascular risk.

Key points

? Iterative reconstruction reduces the amount of coronary calcium detected. ? Iterative reconstruction potentially changes the calcium-based cardiovascular risk estimation. ? Incidentally, calcium is no longer detectable using iterative reconstruction.     

Sensitive immunodetection of radiotoxicity after iodine-131 therapy for thyroid cancer using γ-H2AX foci of DNA damage in lymphocytes

Purpose

The purpose of our study was to evaluate the degree of radiotoxicity to lymphocytes in thyroid cancer after iodine-131(I-131) therapy using γ-H2AX foci immunodetection.

Methods

This study focused on 15 patients who underwent I-131 therapy for differentiated thyroid cancer after surgery. All patients received 3.7 GBq of I-131. Venous blood samples were collected from each patient before therapy and 4 days thereafter. Lymphocytes were isolated from the blood samples and subjected to γ-H2AX immunofluorescence staining.

Results

The number (mean ± SD) of foci per lymphocyte nucleus was 0.41 ± 0.51 before and 6.19 ± 1.80 after radioiodine therapy, and this difference was statistically significant (P = 0.001 < 0.05). Absorbed doses estimated for the 15 patients were 0.77 ± 0.31 Gy applying standard line in vitro external radiation doses.

Conclusion

γ-H2AX foci immunodetection in lymphocytes may detect radiation-induced DNA damage associated with I-131 therapy for thyroid cancer, and may facilitate estimation of the radiation doses absorbed with this therapy.     

Temporal evolution of administered activity in cardiac gated SPECT and patients’ effective dose: analysis of an historical series

Purpose

Myocardial perfusion imaging contributes >20 % of the average medical radiation exposure to the population in the USA. Imaging protocols able to achieve a radiation exposure ≤9 mSv in 50 % of the studies by 2014 have been recommended. The aim of this study was to analyse the temporal evolution of administered activities in patients scheduled for dual-day ^99mTc tracer gated single photon emission computed tomography (SPECT) and to compare different dose administration protocols in terms of patients’ effective dose.

Methods

Patients evaluated from 1 July 2002 to 31 January 2012 were allocated according to the protocol adopted: group 1: fixed activity according to diagnostic reference level: 740 MBq up to 80 kg (adapted for weight <60 kg); 900 MBq 80–100 kg, 1,110 MBq >100 kg, standard filtered back-projection (FBP) reconstruction; group 2: weight-adjusted activity: 8 MBq/kg up to 1,110 MBq, standard FBP reconstruction; and group 3: 4 MBq/kg, UltraSPECT wide beam reconstruction (WBR) reconstruction. A dual-head Anger camera (GE Helix) was used.

Results

A total of 9,060 patients were allocated to different groups: 4,751 in group 1, 2,844 in group 2 and 1,465 in group 3. The stress?+?rest administered activity was 1,617?±?180 in group 1, 1,136?±?260 in group 2 and 682?±?164 MBq in group 3 (all p?<?0.001). Patients’ effective dose was 13.7?±?3 in group 1, 9.5?±?2.8 in group 2 and 5.7?±?1.6 mSv in group 3 (all p?<?0.001). The 50th percentile was 12.6 in group 1, 9.1 in group 2 and 5.3 mSv in group 3. The effective dose received by the dedicated cardiologists was 2.1, 1.5 and 1.0 μSv/exam in group 1, group 2 and group 3 periods, respectively (all p?<?0.001).

Conclusion

A significant reduction over time in the administered activity for gated SPECT was achieved; accordingly, a significant reduction in patients’ exposure was obtained. A simple weight-adjusted strategy with 8 MBq/kg immediately fulfils the recommendations to limit exposure. In selected group 3 patients, a stress-only strategy allows for studies with <3 mSv exposure. Thus, at least the adoption of a new reconstruction algorithm is strongly encouraged, and suggested tracer activities for cardiac gated SPECT are to be revised.