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124I PET-based 3D-RD dosimetry for a pediatric thyroid cancer patient: real-time treatment planning and methodologic comparison.

ABSTRACT: Patient-specific 3-dimensional radiobiologic dosimetry (3D-RD) was used for (131)I treatment planning for an 11-y-old girl with differentiated papillary thyroid cancer, heavy lung involvement, and cerebral metastases. (124)I PET was used for pharmacokinetics. Calculation of the recommended administered activity, based on lung toxicity constraints, was performed in real time (i.e., during the data-acquisition interval). The results were available to the physician in time to influence treatment; these estimates were compared with conventional dosimetry methodologies. In subsequent, retrospective analyses, the 3D-RD calculations were expanded to include additional tumor dose estimates, and the conventional methodologies were reexamined to reveal the causes of the differences observed. A higher recommended administered activity than by an S-value-based method with a favorable clinical outcome was obtained. This approach permitted more aggressive treatment while adhering to patient-specific lung toxicity constraints. A retrospective analysis of the conventional methodologies with appropriate corrections yielded absorbed dose estimates consistent with 3D-RD.

SUBMITTER: Hobbs RF

PROVIDER: S-EPMC2844448 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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124I PET-based 3D-RD dosimetry for a pediatric thyroid cancer patient: real-time treatment planning and methodologic comparison.

Hobbs Robert F RF Wahl Richard L RL Lodge Martin A MA Javadi Mehrbod S MS Cho Steve Y SY Chien David T DT Ewertz Marge E ME Esaias Caroline E CE Ladenson Paul W PW Sgouros George G

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20091016 11

Patient-specific 3-dimensional radiobiologic dosimetry (3D-RD) was used for (131)I treatment planning for an 11-y-old girl with differentiated papillary thyroid cancer, heavy lung involvement, and cerebral metastases. (124)I PET was used for pharmacokinetics. Calculation of the recommended administered activity, based on lung toxicity constraints, was performed in real time (i.e., during the data-acquisition interval). The results were available to the physician in time to influence treatment; t ...[more]

PMID: 19837771

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Project description:UNLABELLED:Tumor endothelial marker 1 (TEM1/endosialin) is a tumor vascular marker highly overexpressed in multiple human cancers with minimal expression in normal adult tissue. In this study, we report the preparation and evaluation of (124)I-MORAb-004, a humanized monoclonal antibody targeting an extracellular epitope of human TEM1 (hTEM1), for its ability to specifically and sensitively detect vascular cells expressing hTEM1 in vivo. METHODS:MORAb-004 was directly iodinated with (125)I and (124)I, and in vitro binding and internalization parameters were characterized. The in vivo behavior of radioiodinated MORAb-004 was characterized in mice bearing subcutaneous ID8 tumors enriched with mouse endothelial cells expressing hTEM1 and by biodistribution and small-animal immuno-PET studies. RESULTS:MORAb-004 was radiolabeled with high efficiency and isolated in high purity. In vitro studies demonstrated specific and sensitive binding of MORAb-004 to MS1 mouse endothelial cells expressing hTEM1, with no binding to control MS1 cells. (125)I-MORAb-004 and (124)I-MORAb-004 both had an immunoreactivity of approximately 90%. In vivo biodistribution experiments revealed rapid, highly specific and sensitive uptake of MORAb-004 in MS1-TEM1 tumors at 4 h (153.2 ± 22.2 percentage injected dose per gram [%ID/g]), 24 h (127.1 ± 42.9 %ID/g), 48 h (130.3 ± 32.4 %ID/g), 72 h (160.9 ± 32.1 %ID/g), and 6 d (10.7 ± 1.8 %ID/g). Excellent image contrast was observed with (124)I-immuno-PET. MORAb-004 uptake was statistically higher in TEM1-positive tumors than in control tumors. Binding specificity was confirmed by blocking studies using excess nonlabeled MORAb-004. CONCLUSION:In our preclinical model, with hTEM1 exclusively expressed on engineered murine endothelial cells that integrate into the tumor vasculature, (124)I-MORAb-004 displays high tumor-to-background tissue contrast for detection of hTEM1 in easily accessible tumor vascular compartments. These studies strongly suggest the clinical utility of (124)I-MORAb-004 immuno-PET in assessing TEM1 tumor-status.

Project description:Patients with metastatic differentiated thyroid cancer (DTC) may be prepared using either thyroid-stimulating hormone withdrawal (THW) or recombinant human thyroid-stimulating hormone (rhTSH) injections before 131I administration for treatment. The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124I PET/CT-based dosimetry for 131I therapy of metastatic DTC when the same patient was prepared with and imaged after both THW and rhTSH injections. Methods: Four DTC patients at MedStar Washington Hospital Center were first prepared using the rhTSH method and imaged by 124I PET/CT at 2, 24, 48, 72, and 96 h after administration of approximately 30-63 MBq of 124I. After 5-8 wk, the same patients were prepared using the THW method and imaged as before. The 124I PET/CT images acquired as part of a prospective study were used to perform retrospective dosimetric calculations for 131I therapy for the normal organs with the dosimetry package 3D-RD. The absorbed doses from 131I for the lungs, liver, heart, kidneys, and bone marrow were obtained for each study (rhTSH and THW). Twenty-two lesions in 3 patients were identified. The contours were drawn on each PET image of each study. Time-integrated activity coefficients were calculated and used as input in OLINDA/EXM sphere dose calculator to obtain the absorbed dose to tumors. Results: The THW-to-rhTSH organ absorbed dose ratio averaged over 5 organs for the first 3 patients was 1.5, 2.5, and 0.64, respectively, and averaged over 3 organs for the fourth patient was 1.1. The absorbed dose per unit administered activity to the bone marrow was 0.13, 0.086, 0.33, and 0.068 mGy/MBq after rhTSH and 0.11, 0.14, 0.22, and 0.080 mGy/MBq after THW for each patient, respectively. With the exception of 3 lesions of 1 patient, the absorbed dose per unit administered activity of 131I was higher in the THW study than in the rhTSH study. The ratio of the average tumor absorbed dose after stimulation by THW compared with stimulation by rhTSH injections was 3.9, 27, and 1.4 for patient 1, patient 2, and patient 3, respectively. The ratio of mean tumor to bone marrow absorbed dose per unit administered activity of 131I, after THW and rhTSH, was 232 and 62 (patient 1), 12 and 0.78 (patient 2), and 22 and 11 (patient 3), respectively. Conclusion: The results suggest a high patient variability in the overall absorbed dose to the normal organs per MBq of 131I administered, between the 2 TSH stimulation methods. The tumor-to-dose-limiting-organ (bone marrow) absorbed dose ratio, that is, the therapeutic index, was higher in the THW-aided than rhTSH-aided administrations. Additional comparison for tumor and normal organ absorbed dose in patients prepared using both methods is needed before definitive conclusions may be drawn regarding rhTSH versus THW patient preparation methods for 131I therapy of metastatic DTC.

Project description:PurposeTo investigate the dosimetric characteristics of PRESAGEREU dosimeters.MethodsCommercially available PRESAGEREU dosimeters (size of 10 mm × 10 mm × 45 mm) were divided into two groups, with one of the groups placed at room temperature of 22°C (RT group) and another group placed at low temperature of 10°C (LT group). A total of 3 dosimeters (set of dosimeters) were irradiated at a time, with doses of 1 Gy, 2 Gy, 4 Gy, 8 Gy, 12 Gy, 16 Gy, and 20 Gy, at a nominal dose rate of 400 MU/min at temperature of 22°C. The dosimeters were irradiated three additional times by delivering the same doses as those during the initial irradiations (4 irradiation cycles). Optical density (OD) was assessed using optical CT scanning.ResultsConsidering both linearity and sensitivity of the OD curves, R2 above 0.95 and sensitivity above 0.04 ?OD/Gy were observed at the 1st irradiation (reading time ? 6 h) and 2nd irradiation (reading time = 0.5 h) for the RT group. For the LT group, those values were observed at the 1st irradiation (reading time ? 2 h), and the 3rd and 4th irradiations (both reading times = 0.5 h). Considering the reproducibility of signals in response to the same dose, dosimeters in the RT group showed average deviations among dosimeters less than 5% (the 1st and 2nd irradiations at the reading time of 0.5 h), while for dosimeters in the LT group showed average deviations among dosimeters less than 6% (the 3rd and 4th irradiations at the reading time of 0.5 h). For the rest, the OD curves were not linear, sensitivities of the dosimeters were lower than 0.04 ?OD/Gy, and OD deviations at the same dose were larger than 6%.ConclusionsAt room temperature, PRESAGEREU dosimeters could be used for dose measurement only for up to two dose measurement sessions. At low temperatures, usage of PRESAGEREU dosimeters for dose measurement seems to be possible from the 3rd irradiation. When reusing PRESAGEREU dosimeters, the OD curve should be re-defined for every measurement session because the shape of this curve depends on the irradiation history.

Dataset Information

124I PET-based 3D-RD dosimetry for a pediatric thyroid cancer patient: real-time treatment planning and methodologic comparison.

Publications

124I PET-based 3D-RD dosimetry for a pediatric thyroid cancer patient: real-time treatment planning and methodologic comparison.

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