Development of [64Cu]Cu-NODAGA-RGD-BBN as a Novel Radiotracer for Dual Integrin and GRPR-targeted Tumor PET Imaging.

BACKGROUND: In this study, [64Cu]Cu-NODAGA-RGD-BBN was prepared and its preclinical assessments were evaluated for PET imaging of GRPR overexpressing tumors. METHODS: NODAGA-RGD-BBN heterodimer peptide was successfully labeled with cyclotronproduced copper-64 at optimized conditions. The radiochemical purity of the radiotracer was checked by HPLC and RTLC methods. The stability of the radiolabeled compound was assessed in PBS (4°C) and in human blood serum (37°C). Binding affinity and internalization of [64Cu]Cu-NODAGA-RGD-BBN were studied on PC3, LNCaP, and CHO cell lines. The biodistribution of the radiotracer was evaluated in normal and tumor-bearing mice. RESULTS: [64Cu]Cu-NODAGA-RGD-BBN was prepared with radiochemical purity >99 ± 0.7% (HPLC/ITLC) and specific activity of 18.5 ± 2.2 TBq/mmol. The radiotracer showed high stability in PBS (95 ± 1.05%) and in human blood serum (96 ± 1.24%) and, high affinity to the GRP expressing tumor cells. [64Cu]Cu-NODAGA-RGD-BBN showed hydrophilic (log p = -1.14) and agonistic nature. The biodistribution and imaging studies demonstrated high uptake at the tumor site at all intervals post-injection and 3-4 h post-injection can be considered an appropriate time of imaging. CONCLUSION: The results indicated that [64Cu]Cu-NODAGA-RGD-BBN radiolabeled heterodimer peptide can be considered as a high-potential agent for PET imaging of GRPRoverexpressing tumors.

75Se - A promising alternative to 192Ir for potential use in the skin cancer brachytherapy: A Monte Carlo simulation study using FLUKA code.

This study aimed to evaluate the possibility of utilizing the HDR 75Se source for skin cancer brachytherapy. In this work, based on the BVH-20 skin applicator, two cup-shaped applicators, without and with the flattening filter, were modeled. To obtain the optimal flattening filter shape, an approach based on the MC simulation in combination with an analytical estimation was used. Then, the dose distributions for 75Se-applicators were generated using MC simulations in water, and their dosimetric characterizations such as flatness, symmetry, and penumbra were evaluated. Furthermore, the radiation leakage in the backside of the applicators was estimated by additional MC simulation. Finally, to evaluate the treatment times, calculations were performed for two 75Se-applicators assuming 5 Gy per fraction. The flatness, symmetry, and penumbra values for the 75Se-applicator without the flattening filter were estimated to be 13.7%, 1.05, and 0.41 cm respectively. The corresponding values for 75Se-applicator with the flattening filter were estimated to be 1.6%, 1.06, and 0.10 cm respectively. The radiation leakage value at a distance of 2 cm from the applicator surface was calculated to be 0.2% and 0.4% for the 75Se-applicator without and with the flattening filter respectively. Our results showed that the treatment time for the 75Se-applicator is comparable with that of the 192Ir-Leipzig applicator. The findings revealed that the dosimetric parameters of the 75Se applicator are comparable with the 192Ir skin applicator. Overall, the 75Se source can be an alternative to 192Ir sources for HDR brachytherapy of skin cancer.

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.

Evaluation of effectiveness of equivalent dose during proton boron fusion therapy (PBFT) for brain cancer: A Monte Carlo study.

Recently it has been suggested that the presence of boron-11 during proton therapy leads to a significant dose increasement in the BUR. Three high-LET alpha particles with an average energy of 4 MeV are generated at the point of interaction between proton and boron-11. Nevertheless, the cross-section of p+B11→3α interaction is negligible and dose increasement is unlikely. The purpose of this study is dose evaluation of the proton therapy with and without the boron-11. All simulations were performed using MCNPX 2.6.0 code at the Snyder head phantom. At the elderly stage, the range of Bragg-peaks was adapted to the tumor volume, with and without boron-11. Then, the different concentrations of boron-11 were assumed including 65,500,103,105,2.5×105 and 5×105ppm in the tumor region. To investigate the maximum effectiveness of PBFT (proton boron fusion therapy), the entire tumor was assumed full of boron-11, and the dose components were calculated. Consequently, In the best case, the maximum dose amplification was less than 5%, in which the entire tumor was assumed full boron-11. The total number of alpha particles generated from p+B11→3α interaction is negligible. As well as the presence of boron-11 during the proton therapy makes that the Bragg-peaks happen in greater depth. Hence, from the Monte Carlo standpoint, the effectiveness of the proton boron fusion therapy is not related to the alpha particles because the dose component of alpha particles is negligible.

Monte Carlo characterization of biocompatible beta-emitting 90Y glass seed incorporated with the radionuclide 153Sm as a SPECT marker for brachytherapy applications.

A glass seed consisting of the ß--emitting radionuclide 90Y incorporated with radionuclide 153Sm as SPECT marker is proposed for potential application in brachytherapy in order to reduce the undesirable dose to healthy adjacent organs. The aim of this work is to determine the dosimetric characteristics, as suggested in the AAPM TG-60/TG-149 reports, for this seed using Monte Carlo simulation. Monte Carlo codes MCNP5, EGSnrc, and FLUKA were used to calculate the absorbed dose distribution around the seed. Dosimetric parameters, such as reference absorbed dose rate, radial dose function, and one-dimensional (1D) and two-dimensional (2D) anisotropy functions, were obtained. The computational results from these three codes are in agreement within 5.4% difference on average. The absorbed dose rate at the reference point was estimated to be 5.01 cGy h-1 µCi-1 and self absorption of YAS glass seed amounted to 30.51%. The results showed that, with thermal neutron bombardment of 5 hours in a typical flux, sufficient activity for applications in brachytherapy may be achieved. With a 5 mCi initial activity, the total dose of a YAS glass seed was estimated to be 1.38 Gy at 1.0 cm from the seed center. Comparing with gamma emitting seeds, the 90Y seed could reduce undesirable doses to adjacent organs, because of the rapid dose falloff of beta ray. Because of the high R90 value of 5.5 mm, fewer number of 90Y seeds will be required for an interstitial brachytherapy treatment using permanent implant, in comparison with other beta-emitting seeds. The results would be helpful in the development of the radioactive implants using 90Y glass seeds for the brachytherapy treatment.