Evaluation of dosimetric functions for a new 169 Yb HDR Brachytherapy Source.

169 Yb has been recently used as an HDR brachytherapy source for cancer treatment. In this paper, dosimetric parameters of a new design of 169 Yb HDR brachytherapy source were determined by Monte Carlo (MC) method and film dosimetry. In this new source, the radioactive core has been encapsulated twice for safety purposes. The calculations of dosimetric parameters carried out using MC simulation in water and air phantom. In order to exclude photon contamination's cutoff energy, δ was set at 10 keV. TG-43U1 data dosimetric, including Sk , Λ, g(r), F(r, θ) was computed using outputs from the simulation and their statistical uncertainties were calculated. Dose distribution around the new prototype source in PMMA phantom in the framework of AAPM TG-43 and TG-55 recommendations was measured by Radiochromic film (RCF) Gafchromic EBT3. Obtained air kerma strength, Sk , and the dose rate constant, Λ, from simulation has a value of 1.03U ± 0.03 and 1.21 cGyh-1 U-1  ± 0.03, respectively. The radial dose function was calculated at radial distances between 0.5 and 10 cm with a maximum value of 1.15 ± 0.03 at 5-6 cm distances. The anisotropy functions for radial distances of 0.5-7 cm and angle distances 0° to180° were calculated. The dosimetric data of the new HDR 169 Yb source were compared with another reference source of 169 Yb-HDR and were found that has acceptable compatibility. In addition, the anisotropy function of the MC simulation and film dosimetry method at a distance of 1 cm from this source was obtained and a good agreement was found between the anisotropy results.

A re-activation model for 169Yb intensity modulated brachytherapy sources accounting for spatiotemporal isotopic composition.

BACKGROUND: Intensity modulated brachytherapy based on partially shielded intracavitary and interstitial applicators is possible with a cost-effective 169Yb production method. 169Yb is a traditionally expensive isotope suitable for this purpose, with an average γ-ray energy of 93 keV. Re-activating a single 169Yb source multiple times in a nuclear reactor between clinical uses was shown to theoretically reduce cost by approximately 75% relative to conventional single-activation sources. With re-activation, substantial spatiotemporal variation in isotopic source composition is expected between activations via 168Yb burnup and 169Yb decay, resulting in time dependent neutron transmission, precursor usage, and reactor time needed per re-activation. PURPOSE: To introduce a generalized model of radioactive source production that accounts for spatiotemporal variation in isotopic source composition to improve the efficiency estimate of the 169Yb production process, with and without re-activation. METHODS AND MATERIALS: A time-dependent thermal neutron transport, isotope transmutation, and decay model was developed. Thermal neutron flux within partitioned sub-volumes of a cylindrical active source was calculated by raytracing through the spatiotemporal dependent isotopic composition throughout the source, accounting for thermal neutron attenuation along each ray. The model was benchmarked, generalized, and applied to a variety of active source dimensions with radii ranging from 0.4 to 1.0 mm, lengths from 2.5 to 10.5 mm, and volumes from 0.31 to 7.85 mm3, at thermal neutron fluxes from 1 × 1014 to 1 × 1015 n cm-2 s-1. The 168Yb-Yb2O3 density was 8.5 g cm-3 with 82% 168Yb-enrichment. As an example, a reference re-activatable 169Yb active source (RRS) constructed of 82%-enriched 168Yb-Yb2O3 precursor was modeled, with 0.6 mm diameter, 10.5 mm length, 3 mm3 volume, 8.5 g cm-3 density, and a thermal neutron activation flux of 4 × 1014 neutrons cm-2 s-1. RESULTS: The average clinical 169Yb activity for a 0.99 versus 0.31 mm3 source dropped from 20.1 to 7.5 Ci for a 4 × 1014 n cm-2 s-1 activation flux and from 20.9 to 8.7 Ci for a 1 × 1015 n cm-2 s-1 activation flux. For thermal neutron fluxes ≥2 × 1014 n cm-2 s-1, total precursor and reactor time per clinic-year were maximized at a source volume of 0.99 mm3 and reached a near minimum at 3 mm3. When the spatiotemporal isotopic composition effect was accounted for, average thermal neutron transmission increased over RRS lifetime from 23.6% to 55.9%. A 28% reduction (42.5 days to 30.6 days) in the reactor time needed per clinic-year for the RRS is predicted relative to a model that does not account for spatiotemporal isotopic composition effects. CONCLUSIONS: Accounting for spatiotemporal isotopic composition effects within the RRS results in a 28% reduction in the reactor time per clinic-year relative to the case in which such changes are not accounted for. Smaller volume sources had a disadvantage in that average clinical 169Yb activity decreased substantially below 20 Ci for source volumes under 1 mm3. Increasing source volume above 3 mm3 adds little value in precursor and reactor time savings and has a geometric disadvantage.

Dosimetry investigation of a prototype of 169Yb seed brachytherapy for use in circular stapler.

This study aims to investigate dosimetry parameters for the new design of 169Yb seed in the form of a surgical staple for circular staplers commonly used in the abdominal incision and the esophageal and gastric surgery, which facilitates the precise placement. This seed includes a titanium tube with the inner diameter and outer diameter 0.68 mm and 2.2 mm, respectively, and length of 0.8 mm. Both sides of the tube are closed by titanium wires with the thickness of 0.65 mm by the laser. Natural ytterbium oxide is used after the thermal neutron activation; it is necessary for cooling time of 40 days. The dosimetry parameters were calculated based on the TG-43U1 using Monte Carlo MCNP5 code. The experimental dosimetry was performed by EBT3 radiochromic film to determine 2D dosimetry at near distance of the source and validate the MC code. The dose rate constant of MC calculation was obtained at 1.39cGyh-1U-1 ± 4% with the difference of 5% compared to another study. The dose distribution was symmetrical along the Z-axis and Y-axis (around the seed) and there was a uniform activity inside the tube. The distinction of dose rate was not noticeable at the 90 and 270 degrees on the Z-axis, which indicated a slight effect on staple legs in the matter of delivery dose. However, to understand dose distribution and introduce this source in a pre-clinical study, 3D dosimetry as well as further studying the heterogeneous function is required.

Experimental study of α-particle induced reactions on natural erbium for the production of Auger-emitters 167Tm, 165Er and 169Yb.

The cross sections for nuclear reactions natEr(α,x) were measured in the energy range 60 â†’ 10 MeV using the stacked-foil technique. The experiments were carried out in a wider energy range in comparison with previous works. The results are consistent with other studies and modeling using TENDL-2019. The 167Tm yield was 5.4 MBq/µAh in the range 60 â†’ 30 MeV, and the main long-lived impurity is 168Tm (0.78% in terms of activity). The 165Tm yield is 4.6 MBq/µAh (60 â†’ 40 MeV). 169Yb is formed with a yield of 1.0 MBq/µAh in the energy range 60 â†’ 20 MeV.

Needle-free cervical cancer treatment using helical multishield intracavitary rotating shield brachytherapy with the 169 Yb Isotope.

PURPOSE: To assess the capability of an intracavitary 169 Yb-based helical multishield rotating shield brachytherapy (RSBT) delivery system to treat cervical cancer. The proposed RSBT delivery system contains a pair of 1.25 mm thick platinum partial shields with 45° and 180° emission angles, which travel in a helical pattern within the applicator. METHODS: A helically threaded tandem applicator with a 45° tandem curvature containing a helically threaded catheter was designed. A 0.6 mm diameter 169 Yb source with a length of 10.5 mm was simulated. A 37-patient treatment planning study, based on Monte Carlo dose calculations using MCNP5, was conducted with high-risk clinical target volumes (HR-CTVs) of 41.2-192.8 cm3 (average ± standard deviation of 79.9 ± 35.8 cm3 ). All patients were assumed to receive 25 fractions of 1.8 Gy of external beam radiation therapy (EBRT) before receiving 5 fractions of high-dose-rate brachytherapy (HDR-BT). For each patient, 192 Ir-based intracavitary (IC) HDR-BT, 192 Ir-based intracavitary/interstitial (IC/IS) HDR-BT using a hybrid applicator with eight IS needles, and 169 Yb-based RSBT plans were generated. RESULTS: For the IC, IC/IS, and RSBT treatment plans, 38%, 84%, and 86% of the plans, respectively, met the planning goal of an HR-CTV D90 (minimum dose to hottest 90%) of 85 GyEQD2 (α/ß = 10 Gy). Median (25th percentile, 75th percentile) treatment times for IC, IC/IS, and RSBT were 11.71 (6.62, 15.40) min, 68.00 (45.02, 80.02) min, and 25.30 (13.87, 35.39) min, respectively. 192 Ir activities ranging from 159.1-370 GBq (4.3-10 Ci) and 169 Yb activities ranging from 429.2-999 GBq (11.6-27 Ci) were used, which correspond to the same clinical ranges of dose rates at 1 cm off-source-axis in water. Extra needle insertion and planning time beyond that needed for intracavitary-only approaches was accounted for in the IC/IS treatment time calculations. CONCLUSION: 169 Yb-based RSBT for cervical cancer met the HR-CTV D90 goal of 85 Gy in a greater percentage of the patients considered than IC/IS (86% vs 84%, respectively) and can reduce overall treatment time relative to IC/IS. 169 Yb-based RSBT could be used to replace IC/IS in instances where IC/IS treatment is not available, especially in instances when HR-CTV volumes are ≥30 cm3 .

Direction modulated brachytherapy (DMBT) for treatment of cervical cancer: A planning study with 192 Ir, 60 Co, and 169 Yb HDR sources.

PURPOSE: To evaluate plan quality of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator using 192 Ir, 60 Co, and 169 Yb HDR brachytherapy sources, for various cervical cancer high-risk clinical target volumes (CTVHR ). MATERIALS AND METHODS: The novel DMBT tandem applicator has six peripheral grooves of 1.3-mm diameter along a 5.4-mm thick nonmagnetic tungsten alloy rod. Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of the 192 Ir, 60 Co, and 169 Yb HDR sources in a water phantom against the literature data. 45 clinical cases that were treated using conventional tandem-and-ring applicators with 192 Ir source (192 Ir-T&R) were selected consecutively from intErnational MRI-guided BRAchytherapy in CErvical cancer (EMBRACE) trial. Then, for each clinical case, 3D dose distribution of each source inside the DMBT and conventional applicators were calculated and imported onto an in-house developed inverse planning optimization code to generate optimal plans. All plans generated by the DMBT tandem-and-ring (DMBT T&R) from all three sources were compared to the respective 192 Ir-T&R plans. For consistency, all plans were normalized to the same CTVHR D90 achieved in clinical plans. The D2 cm3 for organs at risk (OAR) such as bladder, rectum, and sigmoid, and D90, D98, D10, V100, and V200 for CTVHR were calculated. RESULTS: In general, plan quality significantly improved when a conventional tandem (Con.T) is replaced with the DMBT tandem. The target coverage metrics were similar across 192 Ir-T&R and DMBT T&R plans with all three sources (P > 0.093). 60 Co-DMBT T&R generated greater hot spots and less dose homogeneity in the target volumes compared with the 192 Ir- and 169 Yb-DMBT T&R plans. Mean OAR doses in the DMBT T&R plans were significantly smaller (P < 0.0084) than the 192 Ir-T&R plans. Mean bladder D2 cm3 was reduced by 4.07%, 4.15%, and 5.13%, for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. Mean rectum (sigmoid) D2 cm3 was reduced by 3.17% (3.63%), 2.57% (3.96%), and 4.65% (4.34%) for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. The DMBT T&R plans with the 169 Yb source generally resulted in the greatest OAR sparing when the CTVHR were larger and irregular in shape, while for smaller and regularly shaped CTVHR (<30 cm3 ), OAR sparing between the sources were comparable. CONCLUSIONS: The DMBT tandem provides a promising alternative to the Con.T design with significant improvement in the plan quality for various target volumes. The DMBT T&R plans generated with the three sources of varying energies generated superior plans compared to the conventional T&R applicators. Plans generated with the 169 Yb-DMBT T&R produced best results for larger and irregularly shaped CTVHR in terms of OAR sparing. Thus, this study suggests that the combination of the DMBT tandem applicator with varying energy sources can work synergistically to generate improved plans for cervical cancer brachytherapy.

Comparison of 192 Ir, 169 Yb, and 60 Co high-dose rate brachytherapy sources for skin cancer treatment.

PURPOSE: To evaluate the possibility of utilizing the high-dose rate (HDR) 169 Yb and 60 Co sources, in addition to 192 Ir, for the treatment of skin malignancies with conical applicators. METHODS: Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of single 169 Yb (4140), 60 Co (Co0.A86), and 192 Ir (mHDR-V2) brachytherapy sources in a water phantom and compared their results against published data. A standard conical tungsten alloy Leipzig-style applicator (Stand.Appl) was used for determination of the dose distributions at various depths with a single dwell position of the HDR sources. The HDR sources were modeled with its long axis parallel to the treatment plane within the opening section of the applicator. The source-to-surface distance (SSD) was 1.6 cm, which included a 0.1 cm thick removable plastic end-cap used for clinical applications. The prescription depth was considered to be 0.3 cm in a water phantom following the definitions in the literature for this treatment technique. Dose distributions generated with the Stand.Appl and the 169 Yb and 60 Co sources have been compared with those of the 192 Ir source, for the same geometry. Then, applicator wall thickness for the 60 Co source was increased (doubled) in MC simulations in order to minimize the leakage dose and penumbra to levels that were comparable to that from the 192 Ir source. For each source-applicator combination, the optimized plastic end-cap dimensions were determined in order to avoid over-dosage to the skin surface. RESULTS: The normalized dose profiles at the prescription depth for the 169 Yb-Stand.Appl and the 60 Co-double-wall applicator were found to be similar to that of the 192 Ir-Stand.Appl, with differences < 2.5%. The percentage depth doses (PDD) for the 192 Ir-, 169 Yb- and 60 Co-Stand.Appl were found to be comparable to the values with the 60 Co-double-walled applicator, with differences < 1.7%. The applicator output-factors at the prescription depth were also comparable at 0.309, 0.316, and 0.298 (cGy/hU) for the 192 Ir-, 169 Yb-Stand.Appl, and 60 Co-double-wall applicators respectively. The leakage dose around the Stand.Appl for distance > 2 cm from the applicator surface was < 5% for 192 Ir, < 1% for 169 Yb, and < 18% for 60 Co relative to the prescription dose. However, using the double-walled applicator for the 60 Co source reduced the leakage dose to around 5% of the prescription dose, which is comparable with that of the 192 Ir source. The optimized end-cap thicknesses for the 192 Ir-, 169 Yb-Stand.Appl, and the 60 Co-double-wall applicator were found to be 1.1, 0.6, and 3.7 mm respectively. CONCLUSIONS: Application of the 169 Yb (with Stand.Appl) or the 60 Co source (with double-wall applicator) has been evaluated as alternatives to the existing 192 Ir source (with Stand.Appl) for the HDR brachytherapy of skin cancer patients. These alternatives enable the clinics that may have 169 Yb or 60 Co sources instead of the 192 Ir source to perform the skin brachytherapy and achieve comparable results. The conical surface applicators must be used with a protective plastic end-cap to eliminate the excess electrons that are created in the source and applicator, in order to avoid skin surface over-dosage. The treatment times for the 60 Co source remain to be determined. Additionally, for 169 Yb, the source needs to be changed on monthly basis due to its limited half-life.

Studies on the development of ¹69Yb-brachytherapy seeds: New generation brachytherapy sources for the management of cancer.

This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm (ϕ) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES. Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74 MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the potential for use in prostate brachytherapy. A protocol to prepare (169)Yb-brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets was also formulated.

Reactor production and electrochemical purification of (169)Er: a potential step forward for its utilization in in vivo therapeutic applications.

INTRODUCTION: The aim of the present study was to develop and demonstrate a viable method for the reactor production of (169)Er with acceptable specific activity using moderate flux reactor and its purification from (169)Yb following electrochemical pathway based on mercury-pool cathode to avail (169)Er in radionuclidically pure form essential for its therapeutic use. METHODS: Erbium-169 was produced in reactor by neutron bombardment of isotopically enriched (98.2% in (168)Er) erbium target at a thermal neutron flux of ~8×10(13) n.cm(-2).s(-1) for 21 d. A thorough optimization of irradiation parameters including neutron flux, irradiation time and target cooling time was carried out. The influence of different experimental parameters for the quantitative removal (169)Yb from (169)Er was investigated, optimized and based on the results; a two-cycle electrochemical separation procedure was adopted. The suitablility of purified (169)Er for application in radiation synovectomy and bone pain palliation was ascertained by carrying out radiolabeling studies with hydroxypaptite (HA) particles and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminomethylene phosphonic acid (DOTMP), respectively. RESULTS: Thermal neutron irradiation of 10mg of isotopically enriched (98.2% in (168)Er) erbium target at a flux of ~8×10(13) n.cm(-2).s(-1) for 21 d followed by a two-step electrochemical separation of (169)Yb impurity yielded ~3.7GBq (100mCi) of (169)Er with a specific activity of ~370MBq/mg (10mCi/mg) and radionuclidic purity of >99.99%. The reliability of this approach was amply demonstrated by performing several production batches, where the performance of each batch remained consistent. The utility of the purified (169)Er was demonstrated in the radiolabeling studies with HA particles and DOTMP, wherein both the radiolabeled products were obtained with high radiolabeling yield (>99%). CONCLUSIONS: A viable strategy for the batch production and purification of (169)Er, suitable for therapeutic applications, has been developed and demonstrated.

On the use of high dose rate Ir192 and Yb169 sources with the MammoSite® radiation therapy system.

Ample literature exists on the dose overestimation by commercially available treatment planning systems in MammoSite® applications using high dose rate Ir192 sources for partial breast brachytherapy as monotherapy, due to their inability to predict the dose reduction caused by the radiographic contrast solution in the balloon catheter. In this work Monte Carlo simulation is used to verify the dose rate reduction in a balloon breast applicator which does not vary significantly with distance and it is 1.2% at the prescription distance for the reference simulated geometry of 10% diluted radiographic contrast media and 2.5cm balloon radius. Based on these findings and the minimal hardening of the initially emitted photon spectrum for Ir192, a simple analytical method is proposed and shown capable for correcting dosimetry planning in clinical applications. Simulations are also performed to assess the corresponding dose reduction in applications of balloon breast applicators using high dose rate Yb169 sources that have recently become available. Results yield a far more significant and distance dependent dose reduction for Yb169 (on the order of 20% at the prescription distance for the abovementioned reference simulation geometry). This dose reduction cannot be accounted for using simple analytical methods as for Ir192 due to the significant hardening of the initially emitted Yb169 photons within the diluted radiographic contrast media. Combined with results of previous works regarding the effect of altered scatter conditions (relative to treatment planning system assumptions) on breast treatment planning accuracy, which is more pronounced for Yb169 relative to Ir192, these findings call for the amendment of dose treatment planning systems before using Yb169 high dose rate sources in balloon breast applicators.