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Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I-MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.

ABSTRACT: PURPOSE:To evaluate detailed organ-based radiation-absorbed dose for planning double high-dose treatment with I-MIBG. METHODS:In a prospective study, 33 patients with high-risk refractory or recurrent neuroblastoma were treated with high-dose I-MIBG. Organ dosimetry was estimated from the first I-MIBG posttherapy imaging and from subsequent I-MIBG imaging prior to the planned second administration. Three serial whole-body scans were performed per patient 2 to 6 days after I-MIBG therapy (666 MBq/kg or 18 mCi/kg) and approximately 0.5, 24, and 48 hours after the diagnostic I-MIBG dose (370 MBq/kg or 10 mCi/1.73 m). Organ radiation doses were calculated using OLINDA. I-MIBG scan dosimetry estimations were used to predict doses for the second I-MIBG therapy and compared with I-MIBG posttherapy estimates. RESULTS:Mean ± SD whole-body doses from I-MIBG and I-MIBG scans were 0.162 ± 112 and 0.141 ± 0.068 mGy/MBq, respectively. I-MIBG and I-MIBG organ doses were variable-generally higher for I-MIBG-projected doses than those projected using posttherapy I-MIBG scans. Mean ± SD doses to liver, heart wall, and lungs were 0.487 ± 0.28, 0.225 ± 0.20, and 0.40 ± 0.26, respectively, for I-MIBG and 0.885 ± 0.56, 0.618 ± 0.37, and 0.458 ± 0.56, respectively, for I-MIBG. Mean ratio of I-MIBG to I-MIBG estimated radiation dose was 1.81 ± 1.95 for the liver, 2.75 ± 1.84 for the heart, and 1.13 ± 0.93 for the lungs. No unexpected toxicities were noted based on I-MIBG-projected doses and cumulative dose limits of 30, 20, and 15 Gy to liver, kidneys, and lungs, respectively. CONCLUSIONS:For repeat I-MIBG treatment planning, both I-MIBG and I-MIBG imaging yielded variable organ doses. However, I-MIBG-based dosimetry yielded a more conservative estimate of maximum allowable activity and would be suitable for planning and limiting organ toxicity with repeat high-dose therapies.

SUBMITTER: Pandit-Taskar N

PROVIDER: S-EPMC5753751 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I-MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.

Pandit-Taskar Neeta N Zanzonico Pat P Hilden Patrick P Ostrovnaya Irina I Carrasquillo Jorge A JA Modak Shakeel S

Clinical nuclear medicine 20171001 10

<h4>Purpose</h4>To evaluate detailed organ-based radiation-absorbed dose for planning double high-dose treatment with I-MIBG.<h4>Methods</h4>In a prospective study, 33 patients with high-risk refractory or recurrent neuroblastoma were treated with high-dose I-MIBG. Organ dosimetry was estimated from the first I-MIBG posttherapy imaging and from subsequent I-MIBG imaging prior to the planned second administration. Three serial whole-body scans were performed per patient 2 to 6 days after I-MIBG t ...[more]

PMID: 28759518

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Project description:UnlabelledFor optimal treatment planning in radionuclide therapy, robust tumor dose-response correlations must be established. Here, fully 3-dimensional (3D) dosimetry was performed coupling SPECT/CT at multiple time points with Monte Carlo-based voxel-by-voxel dosimetry to examine such correlations.MethodsTwenty patients undergoing (131)I-tositumomab for the treatment of refractory B-cell lymphoma volunteered for the study. Sixty tumors were imaged. Activity quantification and dosimetry were performed using previously developed 3D algorithms for SPECT reconstruction and absorbed dose estimation. Tumors were outlined on CT at multiple time points to obtain absorbed dose distributions in the presence of tumor deformation and regression. Equivalent uniform dose (EUD) was calculated to assess the biologic effects of the nonuniform absorbed dose, including the cold antibody effect. Response for correlation analysis was determined on the basis of the percentage reduction in the product of the largest perpendicular tumor diameters on CT at 2 mo. Overall response classification (as complete response, partial response, stable disease, or progressive disease) used for prediction analysis was based on criteria that included findings on PET.ResultsOf the evaluated tumor-absorbed dose summary measures (mean absorbed dose, EUD, and other measures from dose-volume histogram analysis), a statistically significant correlation with response was seen only with EUD (r = 0.36 and P = 0.006 at the individual tumor level; r = 0.46 and P = 0.048 at the patient level). The median value of mean absorbed dose for stable disease, partial response, and complete response patients was 196, 346, and 342 cGy, respectively, whereas the median value of EUD for each of these categories was 170, 363, and 406 cGy, respectively. At a threshold of 200 cGy, both mean absorbed dose and EUD had a positive predictive value for responders (partial response + complete response) of 0.875 (14/16) and a negative predictive value of 1.0 (3/3).ConclusionImproved dose-response correlations were demonstrated when EUD incorporating the cold antibody effect was used instead of the conventionally used mean tumor-absorbed dose. This work demonstrates the importance of 3D calculation and radiobiologic modeling when estimating absorbed dose for correlation with outcome.

Project description:131I-metaiodobenzylguanidine (131I-mIBG) is a targeted radiation therapy developed for the treatment of advanced neuroblastoma. We have previously shown that this patient cohort can be used to predict absorbed dose associated with early 131I exposure, 72 h after treatment. We now expand these studies to identify gene expression differences associated with 131I-mIBG exposure 15 days after treatment. Total RNA from peripheral blood lymphocytes was isolated from 288 whole blood samples representing 59 relapsed or refractory neuroblastoma patients before and after 131I-mIBG treatment. We found that several transcripts predictive of early exposure returned to baseline levels by day 15, however, selected transcripts did not return to baseline. At 72 h, all 17 selected pathway-specific transcripts were differentially expressed. Transcripts CDKN1A (P < 0.000001), FDXR (P < 0.000001), DDB2 (P < 0.000001), and BBC3 (P < 0.000001) showed the highest up-regulation at 72 h after 131I-mIBG exposure, with mean log2 fold changes of 2.55, 2.93, 1.86 and 1.85, respectively. At day 15 after 131I-mIBG, 11 of the 17 selected transcripts were differentially expressed, with XPC, STAT5B, PRKDC, MDM2, POLH, IGF1R, and SGK1 displaying significant up-regulation at 72 h and significant down-regulation at day 15. Interestingly, transcripts FDXR (P = 0.01), DDB2 (P = 0.03), BCL2 (P = 0.003), and SESN1 (P < 0.0003) maintained differential expression 15 days after 131I-mIBG treatment. These results suggest that transcript levels for DNA repair, apoptosis, and ionizing radiation-induced cellular stress are still changing by 15 days after 131I-mIBG treatment. Our studies showcase the use of biodosimetry gene expression panels as predictive biomarkers following early (72 h) and late (15 days) internal 131I exposure. Our findings also demonstrate the utility of our transcript panel to differentiate exposed from non-exposed individuals up to 15 days after exposure from internal 131I.

Dataset Information

Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I-MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.

Publications

Assessment of Organ Dosimetry for Planning Repeat Treatments of High-Dose 131I-MIBG Therapy: 123I-MIBG Versus Posttherapy 131I-MIBG Imaging.

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