Introduction Dose response of 22 patients experiencing mCRPC (metastatic castration-resistant prostate cancer) to 177Lu-PSMA I&T radionuclide therapy was investigated. Dosimetry calculations are used to assess correlations between dosimetric quantities and biomarker values. Methods The patients’ age range was 74 ± 7 years at the time of the investigated treatment cycle, and the mean injected activity was 7416 ± 218 MBq. Planar images at several time points postinjection were used for evaluation of absorbed doses to organs and lesion. 68Ga-PSMA PET/CT follow-up imaging enabled the determination of individual tumor molecular volume (TMV) shrinkage. Changes in 7 different biomarkers after the first treatment cycle were correlated with the calculated absorbed organ and TMV doses, resulting in a total number of 259 investigated correlations. Results Sixty-three TMVs were identified in the bone, lymph node, and liver tissue with an average reduction of 32.3%, 84.7%, and 72.9%, respectively. Absorbed doses per unit of administered activity for organs and lesions show good agreement with previous works (0.77, 0.71, and 0.27 mGy/MBq for parotid gland, kidneys, and liver as well as 4.38, 5.47, and 4.95 mGy/MBq for bone, lymph node, and liver malignancies, respectively). Only 37 of 259 possible correlations turned out to be statistically significant, 26 of which are associated with the absorbed dose of an organ and the decrease of alkaline phosphatases. Conclusions Although treatment with 177Lu-PSMA I&T leads to a big reduction of TMV in patients with mCRPC, the lack of correlations calls for studies using voxel-wise dosimetry based on SPECT/CTs.

Purpose The purpose of this paper is to compare the response of two different types of solid‐state microdosimeters, that is, silicon and diamond, and their uncertainties. A study of the conversion of silicon microdosimetric spectra to the diamond equivalent for microdosimeters with different geometry of the sensitive volumes is performed, including the use of different stopping power databases. Method Diamond and silicon microdosimeters were irradiated under the same conditions, aligned at the same depth in a carbon‐ion beam at the MedAustron ion therapy center. In order to estimate the microdosimetric quantities, the readout electronic linearity was investigated with three different methods, that is, the first being a single linear regression, the second consisting of a double linear regression with a channel transition and last a multiple linear regression by splitting the data into odd and even groups. The uncertainty related to each of these methods was estimated as well. The edge calibration was performed using the intercept with the horizontal axis of the tangent through the inflection point of the Fermi function approximation multi‐channel analyzer spectrum. It was assumed that this point corresponds to the maximum energy difference of particle traversing the sensitive volume (SV) for which the residual range difference in the continuous slowing down approximation is equal to the thickness of the SV of the microdosimeter. Four material conversion methods were explored, the edge method, the density method, the maximum‐deposition energy method and the bin‐by‐bin transformation method. The uncertainties of the microdosimetric quantities resulting from the linearization, the edge calibration and the detectors thickness were also estimated. Results It was found that the double linear regression had the lowest uncertainty for both microdosimeters. The propagated standard (k = 1) uncertainties on the frequency‐mean lineal energy truey¯normalF${\bar{y}}_{\rm{F}}$ and the dose‐mean lineal energy truey¯normalD${\bar{y}}_{\rm{D}}$ values from the marker point, in the spectra, in the plateau were 0.1% and 0.2%, respectively, for the diamond microdosimeter, whilst for the silicon microdosimeter data converted to diamond, the uncertainty was estimated to be 0.1%. In the range corresponding to the 90% of the amplitude of the Bragg Peak at the distal part of the Bragg curve (R90) the uncertainty was found to be 0.1%. The uncertainty propagation from the stopping power tables was estimated to be between 5% and 7% depending on the method. The uncertainty on the truey¯normalF${\bar{y}}_{\rm{F}}$ and truey¯normalD${\bar{y}}_{\rm{D}}$ coming from the thickness of the detectors varied between 0.3% and 0.5%. Conclusion This article demonstrate that the linearity of the readout electronics affects the microdosimetric spectra with a difference in truey¯normalF${\bar{y}}_{\rm{F}}$ values between the different linearization methods of up to 17.5%. The combined uncertainty was dominated by the uncertainty of stopping power o...

Purpose:The accurate knowledge of the effective point of measurement (P eff ) is particularly important for measurements in proximity to high dose gradients such as in the distal fall-off of particle beams. For plane-parallel ionization chambers (ICs), P eff is well known and located at the center of the inner surface of the entrance window. For cylindrical ICs, P eff is shifted from the chamber's center toward the beam source. According to IAEA TRS-398, this shift can be calculated as 0.75⋅r cyl for light ions with r cyl being the radius of the cavity. For proton beams and in absence of a dose gradient, no shift is recommended. We have experimentally determined P eff for the 0.125 cc Semiflex IC in both proton and carbon ion beams. Methods: The first method consisted of simultaneous irradiation of a planeparallel IC and the Semiflex in a 4-cm wide spread-out Bragg peak.In the second method, a single-energy beam was used, and both ICs were positioned successively at the same measurement depths. For both approaches, the shift of the distal edge of the depth ionization distributions recorded by the two chambers at different reference points was used to calculate P eff of the Semiflex. Both methods were applied in carbon ion beams, and only the latter was applied in proton beams. Results: Both methods yielded a similar P eff for carbon ions, 0.88⋅r cyl , and 0.84⋅r cyl , which results in a difference of only 0.1 mm. The difference to the recommended value of 0.75⋅r cyl is 0.4 and 0.3 mm, respectively, which is larger than the positioning uncertainty. In the proton beam, a P eff of 0.92⋅r cyl was obtained. Conclusions: The P eff for the 0.125 cc Semiflex IC is shifted further from the cavity center as recommended by IAEA TRS-398 for light ions, with the shift for proton beams being even larger than for carbon ion beams.

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Chondrosarcomas are particularly difficult to treat due to their resistance to chemotherapy and radiotherapy. However, particle therapy can enhance local control and patient survival rates. To improve our understanding of the basic cellular radiation response, as a function of dose and linear energy transfer (LET), we developed a novel water phantom-based setup for cell culture experiments and characterized it dosimetrically. In a direct comparison, human chondrosarcoma cell lines were analyzed with regard to their viability, cell proliferation, cell cycle, and DNA repair behavior after irradiation with X-ray, proton, and carbon ions. Our results clearly showed that cell viability and proliferation were inhibited according to the increasing ionization density, i.e., LET, of the irradiation modes. Furthermore, a prominent G2/M arrest was shown. Gene expression profiling proved the upregulation of the senescence genes CDKN1A (p21), CDKN2A (p16NK4a), BMI1, and FOXO4 after particle irradiation. Both proton or C-ion irradiation caused a positive regulation of the repair genes ATM, NBN, ATXR, and XPC, and a highly significant increase in XRCC1/2/3, ERCC1, XPC, and PCNA expression, with C-ions appearing to activate DNA repair mechanisms more effectively. The link between the physical data and the cellular responses is an important contribution to the improvement of the treatment system.