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.

Optimization of equipment and methodology for whole body activity retention measurements in children undergoing targeted radionuclide therapy.

Accurate measurements of whole-body activity retention of patients during radionuclide therapy are essential for two reasons: First, they enable the correct radiation protection advice to be given and second, they permit the accurate determination of the absorbed whole-body dose delivered during therapy. This, in turn, allows treatment planning to be carried out for future radionuclide therapy on an individual patient basis, and also enables the investigation of the potential correlation of absorbed dose with treatment outcome in groups of patients. There are significant difficulties associated with taking whole-body retention measurements of children, especially when they are very young and/or unwell. It is essential to carry these out in a way that minimises disturbance to the child while still providing good quality data. To accomplish this, we have aimed to optimize the following aspects of the procedure: (i) the environment in which the measurements are performed; (ii) the equipment--which includes the recent installation of a specially designed whole-body activity monitoring system for these patients; and (iii) the methodology for calculating the absorbed dose. These improvements have allowed large numbers of accurate and reproducible whole-body measurements to be collected following patient administrations. This has enabled the identification of more phases of radionuclide excretion during therapy than had previously been observed. These data have been used for radiation protection advice and treatment planning. Two (2) patients were given multiple radionuclide treatments and we were able to compare the whole-body doses delivered.

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.

The effect of energy and source location on gamma camera intrinsic and extrinsic spatial resolution: an experimental and Monte Carlo study.

Quantification of nuclear medicine image data is a prerequisite for personalized absorbed dose calculations and quantitative biodistribution studies. The spatial response of a detector is a governing factor affecting the accuracy of image quantification, and the aim of this work was to model this impact. To simulate spatial response, a value for the intrinsic spatial resolution (R(intrinsic)) of the gamma camera is needed. R(intrinsic) for (99m)Tc was measured over the field of view (FOV) and an experimental setup was designed to measure R(intrinsic) for radioisotopes with higher photon energies. Monte Carlo (MC) simulations, using the codes SIMIND and GATE, were used to investigate the extrinsic effect of R(intrinsic) as a function of energy and its variation across the FOV. A method was developed to calculate energy-dependent blurring values for input to MC simulations, by separate consideration of the Compton scatter and photoelectric effect in the crystal and statistical variation in the signal. Inclusion of energy-specific blurring values in simulations showed excellent agreement with experimental measurements. The maximum pixel count rate can change by up to 18% when imaged at two different points in the FOV, and errors in the maximum pixel count rate of up to 11% were shown if a blurring value for (99m)Tc was used for simulations of (131)I. We demonstrate that the accuracy of MC simulations of gamma cameras can be significantly improved by accounting for the effect of energy on intrinsic spatial resolution.