Experimental validation of Monte Carlo dosimetry for therapeutic beta emitters with radiochromic film in a 3D-printed phantom.

PURPOSE: Validation of dosimetry software, such as Monte Carlo (MC) radiation transport codes used for patient-specific absorbed dose estimation, is critical prior to their use in clinical decision making. However, direct experimental validation in the clinic is generally not performed for low/medium-energy beta emitters used in radiopharmaceutical therapy (RPT) due to the challenges of measuring energy deposited by short-range particles. Our objective was to design a practical phantom geometry for radiochromic film (RF)-based absorbed dose measurements of beta-emitting radionuclides and perform experiments to directly validate our in-house developed Dose Planning Method (DPM) MC code dedicated to internal dosimetry. METHODS: The experimental setup was designed for measuring absorbed dose from beta emitters that have a range sufficiently penetrating to ∼200 µm in water as well as to capture any photon contributions to absorbed dose. Assayed 177 Lu and 90 Y liquid sources, 13-450 MBq estimated to deliver 0.5-10 Gy to the sensitive layer of the RF, were injected into the cavity of two 3D-printed half-cylinders that had been sealed with 12.7 µm or 25.4 µm thick Kapton Tape. A 3.8 × 6 cm strip of GafChromic EBT3 RF was sandwiched between the two taped half-cylinders. After 2-48 h exposures, films were retrieved and wipe tested for contamination. Absorbed dose to the RF was measured using a commercial triple-channel dosimetry optimization method and a calibration generated via 6 MV photon beam. Profiles were analyzed across the central 1 cm2 area of the RF for validation. Eleven experiments were completed with 177 Lu and nine with 90 Y both in saline and a bone equivalent solution. Depth dose curves were generated for 177 Lu and 90 Y stacking multiple RF strips between a single filled half-cylinder and an acrylic backing. All experiments were modeled in DPM to generate voxelized MC absorbed dose estimates. We extended our study to benchmark general purpose MC codes MCNP6 and EGSnrc against the experimental results as well. RESULTS: A total of 20 experiments showed that both the 3D-printed phantoms and the final absorbed dose values were reproducible. The agreement between the absorbed dose estimates from the RF measurements and DPM was on average -4.0% (range -10.9% to 3.2%) for all single film 177 Lu experiments and was on average -1.0% (range -2.7% to 0.7%) for all single film 90 Y experiments. Absorbed depth dose estimates by DPM agreed with RF on average 1.2% (range -8.0% to 15.2%) across all depths for 177 Lu and on average 4.0% (range -5.0% to 9.3%) across all depths for 90 Y. DPM absorbed dose estimates agreed with estimates from EGSnrc and MCNP across the board, within 4.7% and within 3.4% for 177 Lu and 90 Y respectively, for all geometries and across all depths. MC showed that absorbed dose to RF from betas was greater than 92% of the total (betas + other radiations) for 177 Lu, indicating measurement of dominant beta contribution with our design. CONCLUSIONS: The reproducible results with a RF insert in a simple phantom designed for liquid sources demonstrate that this is a reliable setup for experimentally validating dosimetry algorithms used in therapies with beta-emitting unsealed sources. Absorbed doses estimated with the DPM MC code showed close agreement with RF measurement and with results from two general purpose MC codes, thereby validating the use of this algorithms for clinical RPT dosimetry.

Cost-Savings Analysis of Renal Scintigraphy, Stratified by Renal Function Thresholds: Mercaptoacetyltriglycine Versus Diethylene Triamine Penta-Acetic Acid.

PURPOSE: To determine the financial implications of switching technetium (Tc)-99m mercaptoacetyltriglycine (MAG-3) to Tc-99m diethylene triamine penta-acetic acid (DTPA) at certain renal function thresholds before renal scintigraphy. METHODS: Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant, retrospective, cohort study. Consecutive adult subjects (27 inpatients; 124 outpatients) who underwent MAG-3 renal scintigraphy, in the period from July 1, 2012 to June 30, 2013, were stratified retrospectively by hypothetical serum creatinine and estimated glomerular filtration rate (eGFR) thresholds, based on pre-procedure renal function. Thresholds were used to estimate the financial effects of using MAG-3 when renal function was at or worse than a given cutoff value, and DTPA otherwise. Cost analysis was performed with consideration of raw material and preparation costs, with radiotracer costs estimated by both vendor list pricing and proprietary institutional pricing. The primary outcome was a comparison of each hypothetical threshold to the clinical reality in which all subjects received MAG-3, and the results were supported by univariate sensitivity analysis. RESULTS: Annual cost savings by serum creatinine threshold were as follows (threshold given in mg/dL): $17,319 if ≥1.0; $33,015 if ≥1.5; and $35,180 if ≥2.0. Annual cost savings by eGFR threshold were as follows (threshold given in mL/min/1.73 m(2)): $21,649 if ≤60; $28,414 if ≤45; and $32,744 if ≤30. Cost-savings inflection points were approximately 1.25 mg/dL (serum creatinine) and 60 mL/min/1.73m(2) (eGFR). Secondary analysis by proprietary institutional pricing revealed similar trends, and cost savings of similar magnitude. Sensitivity analysis confirmed cost savings at all tested thresholds. CONCLUSIONS: Reserving MAG-3 utilization for patients who have impaired renal function can impart substantial annual cost savings to a radiology department.

Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma.

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining (131)I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received (131)I-MIBG 12 mCi/kg on day -21, followed by carboplatin (1,500 mg/m(2)), etoposide (800 mg/m(2)), and melphalan (210 mg/m(2)) administered from day -7 to day -4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated. RESULTS: The (131)I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil (> or = 0.5 x 10(3)/microL) and platelet (> or = 20 x 10(3)/microL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation. CONCLUSION: Treatment with (131)I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.