SOLLID - a single centre study to develop methods to investigate the effects of low radiation doses within nuclear medicine, to enable multicentre epidemiological investigations.

There is continuing debate concerning the risks of secondary malignancies from low levels of radiation exposure. The current model used for radiation protection is predicated on the assumption that even very low levels of exposure may entail risk. This has profound implications for medical procedures involving ionising radiation as radiation doses must be carefully monitored, and for diagnostic procedures are minimised as far as possible. This incurs considerable expense. The SOLLID study (ClinicalTrials.gov Identifier: NCT03580161) aims to develop the methodology to enable a large-scale epidemiological investigation of the effect of radiopharmaceutical administrations to patients undergoing diagnostic nuclear medicine procedures. Patients will undergo a series of scans in addition to that acquired as standard of care to enable the radiation doses delivered to healthy organs to be accurately calculated. Detailed analysis will be performed to determine the uncertainty in the radiation dose calculations as a function of the number and type of scans acquired. It is intended that this will inform a subsequent long-term multicentre epidemiological study that would address the question definitively. Secondary aims of the study are to evaluate the range of absorbed doses that are delivered from diagnostic nuclear medicine procedures and to use current risk models to ascertain the relative risks from these administrations.

Standardised quantitative radioiodine SPECT/CT Imaging for multicentre dosimetry trials in molecular radiotherapy.

The SEL-I-METRY trial (EudraCT No 2015-002269-47) is the first multicentre trial to investigate the role of 123I and 131I SPECT/CT-based tumour dosimetry to predict response to radioiodine therapy. Standardised dosimetry methodology is essential to provide a robust evidence-base for absorbed dose-response thresholds for molecular radiotherapy (MRT). In this paper a practical standardised protocol is used to establish the first network of centres with consistent methods of radioiodine activity quantification. Nine SPECT/CT systems at eight centres were set-up for quantitative radioiodine imaging. The dead-time of the systems was characterised for up to 2.8 GBq 131I. Volume dependent calibration factors were measured on centrally reconstructed images of 123I and 131I in six (0.8-196 ml) cylinders. Validation of image quantification using these calibration factors was performed on three systems, by imaging a 3D-printed phantom mimicking a patient's activity distribution. The percentage differences between the activities measured in the SPECT/CT image and those measured by the radionuclide calibrator were calculated. Additionally uncertainties on the SPECT/CT-based activities were calculated to indicate the limit on the quantitative accuracy of this method. For systems set-up to image high 131I count rates, the count rate versus activity did not peak below 2.8 GBq and fit a non-paralysable model. The dead-times and volume-dependent calibration factors were comparable between systems of the same model and crystal thickness. Therefore a global calibration curve could be fitted to each. The errors on the validation phantom activities' were comparable to the measurement uncertainties derived from uncertainty analysis, at 10% and 16% on average for 123I and 131I respectively in a 5 cm sphere. In conclusion, the dead-time and calibration factors varied between centres, with different models of system. However, global calibration factors may be applied to the same system model with the same crystal thickness, to simplify set-up of future multi-centre MRT studies.

Compartmental Model for 223Ra-Dichloride in Patients With Metastatic Bone Disease From Castration-Resistant Prostate Cancer.

PURPOSE: 223Ra-Dichloride is used for treatment of patients with metastatic bone disease from castration-resistant prostate cancer. The uptake and mechanism of action of 223Ra-Dichloride is not well understood. The aim of this work was to develop a compartmental model for 223Ra-Dichloride in patients to improve understanding of the underlying mechanisms. METHODS AND MATERIALS: A compartmental model was developed based on activity retention data from 6 patients (2 treatments of 110 kBq/kg 223Ra-Dichloride) for plasma, bone surfaces, small intestines, large intestines, and excretion data. Rate constants were extracted. Rate constant variability between patients and treatments was assessed. A population model was proposed and compared with the established International Commission on Radiological Protection-67 compartmental model. RESULTS: A single bone compartment cannot accurately describe activity retention in the skeleton. The addition of a second bone compartment improved the fit to skeleton retention data, and the Akaike information criterion decreased. Mean rate constants of 4.0 (range, 1.9-10.9) and 0.15 (0.07-0.39) h-1 were obtained for transport from plasma to first bone compartment and vice versa. Rate constants from first to second bone compartment and back of 0.03 (0.02-0.06) and 0.008 (0.003-0.011) h-1 were calculated. Rate constants for individual patients showed no significant difference between patients and treatments. CONCLUSIONS: The developed compartmental model suggests that 223Ra-Dichloride initially locates at the bone surface and is then incorporated into the bone matrix relatively quickly. This observation could have implications for dosimetry and understanding of the effects of alpha radiation on normal bone tissue. Results suggest that a population model based on patient measurements is feasible.

Improving Transitional Care: The Role of Handoffs and Discharge Checklists in Hematologic Malignancies.

BACKGROUND: Transitional care from inpatient to outpatient settings is a high-risk time for medical errors and missed follow-up appointments. Discharge checklists and handoffs are effective tools that lead to improved quality of care and outcomes. OBJECTIVES: The purpose of this project was to implement an evidence-based discharge checklist and handoff template to improve and standardize transitional care from hospital to home for patients with hematologic malignancies. METHODS: The advanced practice providers (APPs) completed the discharge checklist at least 24 hours prior to discharge. The APPs requested appointments through the electronic health record using the discharge handoff tool. Chi-square analysis and descriptive statistics were used to analyze the data. FINDINGS: Implementation of the discharge checklist resulted in a statistically significant increase in the number of patients who had a follow-up appointment scheduled prior to discharge. The discharge handoff tool standardized communication between inpatient and outpatient providers.

Dosimetry-based treatment for Graves' disease.

OBJECTIVE: The aim of this retrospective study was to assess the long-term outcome of a personalized dosimetry approach in Graves' disease aiming to render patients euthyroid from a planned thyroid absorbed dose of 60 Gy. PATIENTS AND METHODS: A total of 284 patients with Graves' disease were followed prospectively following administration of radioiodine calculated to deliver an absorbed dose of 60 Gy. Patients with cardiac disease were excluded. Outcomes were analysed at yearly intervals for up to 10 years with a median follow-up of 37.5 months. RESULTS: A single radioiodine administration was sufficient to render a patient either euthyroid or hypothyroid in 175 (62%) patients, the remainder requiring further radioiodine. The median radioactivity required to deliver 60 Gy was 77 MBq. Less than 2% patients required 400-600 MBq, the standard activity administered in many centres. In the cohort receiving a single administration, 38, 32 and 26% were euthyroid on no specific thyroid medication at 3, 5 and 10 years, respectively. Larger thyroid volumes were associated with the need for further therapy. The presence of nodules on ultrasonography did not adversely affect treatment outcome. CONCLUSION: A personalized dosimetric approach delayed the long-term onset of hypothyroidism in 26% of patients. This was achieved using much lower administered activities than currently recommended. Future studies will aim to identify those patients who would benefit most from this approach.

Bone lesion absorbed dose profiles in patients with metastatic prostate cancer treated with molecular radiotherapy.

OBJECTIVE: The aim of this study was to calculate the range of absorbed doses that could potentially be delivered by a variety of radiopharmaceuticals and typical fixed administered activities used for bone pain palliation in a cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). The methodology for the extrapolation of the biodistribution, pharmacokinetics and absorbed doses from a given to an alternative radiopharmaceutical is presented. METHODS: Sequential single photon emission CT images from 22 patients treated with 5 GBq of 186Re-HEDP were used to extrapolate the time-activity curves for various radiopharmaceuticals. Cumulated activity distributions for the delivered and extrapolated treatment plans were converted into absorbed dose distributions using the convolution dosimetry method. The lesion absorbed doses obtained for the different treatments were compared using the patient population distributions and cumulative dose-volume histograms. RESULTS: The median lesion absorbed doses across the patient cohort ranged from 2.7 Gy (range: 0.6-11.8 Gy) for 1100 MBq of 166Ho-DOTMP to 21.8 Gy (range: 4.5-117.6 Gy) for 150 MBq of 89Sr-dichloride. 32P-Na3PO4, 153Sm-EDTMP, 166Ho-DOTMP, 177Lu-EDTMP and 188Re-HEDP would have delivered 41, 32, 85, 20 and 64% lower absorbed doses, for the typical administered activities as compared to 186Re-HEDP, respectively, whilst 89Sr-dichloride would have delivered 25% higher absorbed doses. CONCLUSION: For the patient cohort studied, a wide range of absorbed doses would have been delivered for typical administration protocols in mCRPC. The methodology presented has potential use for emerging theragnostic agents. Advances in knowledge: The same patient cohort can receive a range of lesion absorbed doses from typical molecular radiotherapy treatments for patients with metastatic prostate cancer, highlighting the need to establish absorbed dose response relationships and to treat patients according to absorbed dose instead of using fixed administered activities.

Excretion and whole-body retention of radium-223 dichloride administered for the treatment of bone metastases from castration resistant prostate cancer.

OBJECTIVE: The aim of the study was to determine the fraction of administered activity that was excreted and retained by a small cohort of patients who each received treatment with radium-223 dichloride (Ra). Ra is an α-emitting radionuclide that has been approved for use in the treatment of bone metastases that are secondary to castration resistant prostate cancer. PATIENTS AND METHODS: Six patients received two weight-based administrations of Ra 6 weeks apart. Activity excreted in the urine and faeces during the first 48 h following each treatment was assessed by direct counting of the excreta. During the same period the whole-body retention of Ra was also determined using a single probe counting system. The results of the excreta counting and the whole-body counting were compared to determine whether whole-body counting was a suitable surrogate for assessing excretion. Further whole-body retention counts were made at around 3, 4, 7 and 42 days following treatment. RESULTS: Patterns of excretion and retention of Ra varied significantly between patients, but were similar for each patient's pair of treatments. The cumulative maximum activity excreted in the initial 8-h period following the Ra administration was 2.6% that increased to 39% at 48 h. The median excreted activity at ~1 and 6 weeks after treatment was 70 and 86%, respectively. Skeletal retention of Ra at 6 weeks ranged from 11 to 60% of the administered activity.

The potential of 223Ra and 18F-fluoride imaging to predict bone lesion response to treatment with 223Ra-dichloride in castration-resistant prostate cancer.

PURPOSE: The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of 223Ra-dichloride, to assess the relationship between those doses and corresponding 18F-fluoride uptake and to assess the potential of quantitative 18F-fluoride imaging to predict response to treatment. METHODS: Five patients received two intravenous injections of 223Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of 223Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial 223Ra scans. PET/CT imaging using 18F-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline. RESULTS: Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5-11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in 18F-fluoride uptake was demonstrated (r2 = 0.52). A log-linear relationship was demonstrated (r2 = 0.77) between baseline measurements of 18F-fluoride uptake prior to 223Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both 223Ra and 18F-fluoride uptake in lesions (r = 0.75) as well as between 223Ra absorbed dose and 18F-fluoride uptake (r = 0.96). CONCLUSIONS: There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between 223Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of 18F-fluoride in bone metastases is significantly correlated with corresponding uptake of 223Ra, the associated 223Ra absorbed dose and subsequent lesion response to treatment.

A radiobiological model of metastatic burden reduction for molecular radiotherapy: application to patients with bone metastases.

Skeletal tumour burden is a biomarker of prognosis and survival in cancer patients. This study proposes a novel method based on the linear quadratic model to predict the reduction in metastatic tumour burden as a function of the absorbed doses delivered from molecular radiotherapy treatments. The range of absorbed doses necessary to eradicate all the bone lesions and to reduce the metastatic burden was investigated in a cohort of 22 patients with bone metastases from castration-resistant prostate cancer. A metastatic burden reduction curve was generated for each patient, which predicts the reduction in metastatic burden as a function of the patient mean absorbed dose, defined as the mean of all the lesion absorbed doses in any given patient. In the patient cohort studied, the median of the patient mean absorbed dose predicted to reduce the metastatic burden by 50% was 89 Gy (interquartile range: 83-105 Gy), whilst a median of 183 Gy (interquartile range: 107-247 Gy) was found necessary to eradicate all metastases in a given patient. The absorbed dose required to eradicate all the lesions was strongly correlated with the variability of the absorbed doses delivered to multiple lesions in a given patient (r = 0.98, P < 0.0001). The metastatic burden reduction curves showed a potential large reduction in metastatic burden for a small increase in absorbed dose in 91% of patients. The results indicate the range of absorbed doses required to potentially obtain a significant survival benefit. The metastatic burden reduction method provides a simple tool that could be used in routine clinical practice for patient selection and to indicate the required administered activity to achieve a predicted patient mean absorbed dose and reduction in metastatic tumour burden.

InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration.

Phase I/II trials of 186Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival.

PURPOSE: To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit. METHODS: Clinical data from 57 patients who received 2.5-5.1 GBq of 186Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan-Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses. RESULTS: A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10-0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of 186Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004). CONCLUSION: This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose-response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry.

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.

OBJECTIVE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach. MATERIALS AND METHODS: A review of 44 treatments in 25 patients treated with I-mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients. RESULTS: The mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease. CONCLUSION: A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy.

A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of 223Ra-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases.

UNLABELLED: The aim of this single-site, open-label clinical trial was to determine the biodistribution, pharmacokinetics, absorbed doses, and safety from 2 sequential weight-based administrations of (223)Ra-dichloride in patients with bone metastases due to castration-refractory prostate cancer. METHODS: Six patients received 2 intravenous injections of (223)Ra-dichloride, 6 wk apart, at 100 kBq/kg of whole-body weight. The pharmacokinetics and biodistribution as a function of time were determined, and dosimetry was performed for a range of organs including bone surfaces, red marrow, kidneys, gut, and whole body using scintigraphic imaging; external counting; and blood, fecal, and urine collection. Safety was assessed from adverse events. RESULTS: The injected activity cleared rapidly from blood, with 1.1% remaining at 24 h. The main route of excretion was via the gut, although no significant toxicity was reported. Most of the administered activity was taken up rapidly into bone (61% at 4 h). The range of absorbed doses delivered to the bone surfaces from α emissions was 2,331-13,118 mGy/MBq. The ranges of absorbed doses delivered to the red marrow were 177-994 and 1-5 mGy/MBq from activity on the bone surfaces and from activity in the blood, respectively. No activity-limiting toxicity was observed at these levels of administration. The absorbed doses from the second treatment were correlated significantly with the first for a combination of the whole body, bone surfaces, kidneys, and liver. CONCLUSION: A wide range of interpatient absorbed doses was delivered to normal organs. Intrapatient absorbed doses were significantly correlated between the 2 administrations for any given patient. The lack of gastrointestinal toxicity is likely due to the low absorbed doses delivered to the gut wall from the gut contents. The lack of adverse myelotoxicity implies that the absorbed dose delivered from the circulating activity may be a more relevant guide to the potential for marrow toxicity than that due to activity on the bone surfaces.

Patient-specific dosimetry for intracavitary 32P-chromic phosphate colloid therapy of cystic brain tumours.

PURPOSE: (32)P-chromic phosphate colloid treatments of astrocytoma and craniopharyngioma cystic brain tumours in paediatric patients are conventionally based on a sphere model under the assumption of uniform uptake. The aims of this study were to determine the distribution of the absorbed dose delivered by (32)P on a patient-specific basis and to evaluate the accuracy with which this can be predicted from a pretherapy administration of (99m)Tc-Sn colloid. METHODS: Three patients were treated with (32)P-chromic phosphate colloid following (99m)Tc-Sn colloid administrations. Convolution dosimetry was performed using pretherapy and posttherapy sequential SPECT imaging, and verified with EGSnrc Monte Carlo radiation transport simulations. Mean absorbed doses to the cyst wall and dose-volume histograms were also calculated and compared with those obtained by the sphere model approach. RESULTS: Highly nonuniform uptake distributions of both the (99m)Tc and (32)P colloids were observed and characterized by dose-volume histograms to the cyst wall. Mean absorbed doses delivered to the cyst wall, obtained with the convolution method, were on average 21 % (SD 18 %) and 50 % (SD 30 %) lower than those predicted by the (99m)Tc distribution and the uniform assumption of the sphere model, respectively. CONCLUSION: Absorbed doses delivered to the cyst wall by (32)P are more accurately predicted from image-based patient-specific convolution dosimetry than from simple sphere models. These results indicate the necessity to perform personalized treatment planning and verification for intracavitary irradiation of cystic brain tumours treated with radiocolloids. Patient-specific dosimetry can be used to guide the frequency and levels of repeated administrations and would facilitate data collection and comparison to support the multicentre trials necessary to progress this therapy.

Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases.

OBJECTIVE: Ra is an alpha particle emitter that targets areas of increased bone turnover in bone metastases. Alpha particles account for 95% of the 27.8 MeV emitted per decay. Less than 2% of the emissions are from photons. This means that a high absorbed dose will be delivered locally, although the number of photons for imaging will be low. The purpose of this study was to investigate the possibility of quantitative imaging of Ra to enable biodistribution studies. METHODS: A Philips Forte gamma camera, equipped with a medium-energy collimator, was used. Basic imaging parameters were determined from phantom studies, and the accuracy of activity quantification was tested in a phantom study and within a patient study. RESULTS: Imaging parameters were determined for the three most suitable photon peaks from the acquired energy spectrum (82, 154 and 270 keV). Camera sensitivity is constant for circular sources with areas greater than 10 cm. The spatial resolution (full-width at half-maximum) was 1.1 cm for each of the three energy windows. The possibility for quantitative imaging was further investigated for the 82 keV energy window, which showed the highest sensitivity and spatial resolution. A phantom study showed that activity could be quantified to within 10% for a 200 ml volume placed within water containing background activity and to within 50% for a 0.5 ml phantom. Quantification of activity in bone after administrations of 100 kBq/kg of Ra-chloride proved the feasibility of quantitative imaging of patients who have received radionuclide therapy. CONCLUSION: Because of the high-energy deposition of Ra, only a low injected activity is required for therapy, which results in a low count rate for the gamma camera. Nevertheless, this study has demonstrated that it is possible to quantify uptake with a sufficient degree of accuracy to obtain clinically relevant information.

A dose-effect correlation for radioiodine ablation in differentiated thyroid cancer.

PURPOSE: The aim of this study was to determine the range of absorbed doses delivered to thyroid remnants, blood, and red marrow from fixed administrations of radioiodine and to ascertain whether the success of ablation is more dependent on these absorbed doses than on the administered activity. METHODS: Twenty-three patients received 3,000 MBq radioiodine following near-total thyroidectomy. The maximum absorbed dose to remnants was calculated from subsequent single photon emission tomography scans. Absorbed doses delivered to blood and red marrow were calculated from blood samples and from whole-body retention measurements. The protein bound iodine (PBI) was also calculated. RESULTS: Maximum absorbed doses to thyroid remnants ranged from 7 to 570 Gy. Eighteen of the 23 patients had a successful ablation. A significant difference was seen between the absorbed doses delivered to thyroid remnants, blood, and red marrow for those patients that had a successful ablation compared to those with a failed ablation (p = 0.030, p = 0.043 and p = 0.048, respectively). The difference between the PBI values acquired at day 1 and day 6 were also indicative of response (p = 0.074). CONCLUSIONS: A successful ablation is strongly dependent on the absorbed dose to the thyroid remnant. Dosimetry-based personalized treatment can prevent both sub-optimal administrations, which entails further radioiodine therapy, and excessive administration of radioactivity, which increases the potential for radiation toxicity.

Whole-body dosimetry for individualized treatment planning of 131I-MIBG radionuclide therapy for neuroblastoma.

UNLABELLED: The aims of this study were to examine the relationship between whole-body absorbed dose and hematologic toxicity and to assess the most accurate method of delivering a prescribed whole-body absorbed dose in (131)I-metaiodobenzylguanidine ((131)I-MIBG) therapy for neuroblastoma. METHODS: A total of 20 children (1-12 y), 5 adolescents (13-17 y), and 1 adult (20 y) with stage 3 or 4 neuroblastoma were treated to a prescribed whole-body absorbed dose, which in most cases was 2 Gy. Forty-eight administrations of (131)I-MIBG were given to the 26 patients, ranging in activity from 1,759 to 32,871 MBq. For 30 administrations, sufficient data were available to assess the effect of whole-body absorbed dose on hematologic toxicity. Comparisons were made between the accuracy with which a whole-body absorbed dose could be predicted using a pretherapy tracer study and the patient's most recent previous therapy. The whole-body absorbed dose that would have been delivered if the administered activity was fixed (7,400 MBq) or determined using a weight-based formula (444 MBq.kg(-1)) was also estimated. RESULTS: The mean whole-body absorbed dose for patients with grade 4 Common Terminology Criteria for Adverse Events (CTCAE) neutropenia after therapy was significantly higher than for those with grade 1 CTCAE neutropenia (1.63 vs. 0.90 Gy; P = 0.05). There was no correlation between administered activity and hematologic toxicity. Absorbed whole-body doses predicted from previous therapies were within +/-10% for 70% of the cases. Fixed-activity administrations gave the largest range in whole-body absorbed dose (0.30-3.11 Gy). CONCLUSION: The results indicate that even in a highly heterogeneous and heavily pretreated patient population, a whole-body absorbed dose can be prescribed accurately and is a more accurate predictor of hematologic toxicity than is administered activity. Therefore, a whole-body absorbed dose can be used to deliver accurate and reproducible (131)I-MIBG therapy on a patient-specific basis.

Dosimetry for fractionated (131)I-mIBG therapies in patients with primary resistant high-risk neuroblastoma: preliminary results.

This paper describes the development of a protocol for SPECT-based tumor dosimetry for (131)I-mIBG therapy patients with high-risk neuroblastoma. The treatment aims to deliver a whole-body dose of 4 Gy in two fractions. Whole-body retention measurements taken during the first fraction are used to guide the second therapy administration. The tumor dose from 3 patients was assessed by acquiring a minimum of three SPECT scans. Dead-time and triple-energy window scatter corrections were applied. The images were reconstructed using filtered backprojection with a Chang attenuation correction, and a phantom-based calibration factor was used to convert to activity. A monoexponential fit was made to the data, and instantaneous uptake was assumed. Tumor absorbed-dose ratios were used to analyze intrapatient variations, and absolute tumor dosimetry was used to assess interpatient variation. The whole-body dose administered ranged from (3.7 +/- 0.1) Gy to (3.9 +/- 0.3) Gy. This method is more accurate than a weight-based administration method. Despite this, a variation in absorbed tumor dose of 10-103 Gy was observed. All repeat doses were in the same order of magnitude, although 2 patients received a lower tumor dose per MBq from the second therapy owing to a shorter biological half-life. The tumor dosimetry protocol was simple to apply and reproducible, but the errors in image quantitation needed to be evaluated.

Tumor dosimetry on SPECT (186)Re-HEDP scans: variations in the results from the reconstruction methods used.

The aim of this work was to estimate tumor-absorbed doses delivered from the administration of fixed activities of (186)Re-HEDP for the treatment of bone metastases from prostate cancer. The variations and reproducibility in the estimated absorbed dose owing to the reconstruction algorithm used (OSEM vs. FBP) were also analysed. For this aim, correction methods for scatter and attenuation were kept identical, whereas the same calibration data and thresholding techniques were used to obtain quantification. This study was carried out in spinal and pelvic lesions of 7 patients. For comparison, the absorbed doses, based upon the maximum and the mean voxel count, were calculated, resulting in the absorbed dose (maximum): 60 Gy (sigma = 30 Gy) and 33 Gy (sigma = 15 Gy) for OSEM and FBP, respectively, and absorbed dose (mean): 26 Gy (sigma = 12 Gy) and 17 Gy (sigma = 7 Gy) with OSEM and FBP, respectively. We concluded that the administration of fixed activity resulted in a range of absorbed doses, and we showed that, despite using the same approach, the choice of the reconstruction algorithm can result in differences higher than 50% in the estimated tumor-absorbed doses. In conclusion, the need for a standardization of the methodology used for the calculations is emphasized by this work, especially when comparisons between patients and different centers are of interest.