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a 3D surface plot through the central voxel in the CT dose-voxel kernel DVKCT. b 2D cross section through the central voxel in the CT dose-voxel kernel DVKCT. c 3D surface plot through the central voxel in the PET dose-voxel kernel DVKPET. d 2D cross section through the central voxel in the PET dose-voxel kernel DVKPET. The maximum value in all vertical axes and colour bars corresponds to the maximum value of DVKCT
Source publication
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Purpose
To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry.
Materials and methods
A CT calibration phantom was designed containing posts with nominal microsphere concentrati...
Citations
... 6,46 Of note, CT imaging of 90 Y microspheres was also shown to be feasible in preclinical settings. 47 Pertinently, our study utilized Gaussian distributions to represent theoretical image resolutions. Although Gaussian distributions do not capture the individual intricacies of each imaging modality, they may serve as a reference for anticipated differences in the inherent PSFs, voxel sizes, and target volume segmentation among all the imaging modalities used in radioembolization, including CT, MRI, SPECT/CT, and PET/CT. ...
Background
Yttrium‐90 () represents the primary radioisotope used in radioembolization procedures, while holmium‐166 () is hypothesized to serve as a viable substitute for due to its comparable therapeutic potential and improved quantitative imaging. Voxel‐based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S‐value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non‐ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of and dosimetry techniques.
Methods
A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated kernels with published data. The decay spectra of both and were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40 mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16 mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated using reDoseMC.
Results
The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9 MeV in the case of and less than 1% for energies below 1.5 MeV for . Additionally, the validation kernels for VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds (FWHMthreshs${\rm {FWHM}}_\mathrm{thresh}{\rm {s}}$), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for . They were 1.5 mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the reference standard.
Conclusions
reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel‐based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetry analysis.
... However, pre-therapy surrogate dosimetry relies on the assumption that it accurately represents the final 90 Y microsphere distribution as delivered clinically, leading to varied results (Mikell et al 2019). For more accurate dosimetry, the microsphere distribution can be analyzed after treatment with emission-based imaging ( 90 Y PET or Bremsstrahlung SPECT) and potentially soon through CT imaging with the development of radiopaque microspheres (Kappadath et al 2018, Dewaraja et al 2020, Henry et al 2022. Current clinically available dosimetry performed with PET imaging takes advantage of the superior spatial resolution and absolute quantification capabilities compared to SPECT, which is especially relevant for lesion dosimetry. ...
Objective:
90Y selective internal radiation therapy (SIRT) treatment of hepatocellular carcinoma (HCC) can potentially underdose lesions, as identified on post-therapy PET/CT imaging. This study introduces a methodology and explores the feasibility for selectively treating SIRT-underdosed HCC lesions, or lesion subvolumes, with stereotactic body radiation therapy (SBRT) following post-SIRT dosimetry.
Approach:
We retrospectively analyzed post-treatment PET/CT images of 20 HCC patients after 90Y SIRT. Predicted tumor response from SIRT was quantified based on personalized post-therapy dosimetry and corresponding response models. Predicted non-responding tumor regions were then targeted with a hypothetical SBRT boost plan using a framework for selecting eligible tumors and tumor subregions. SBRT boost plans were compared to SBRT plans targeting all tumors irrespective of SIRT dose with the same prescription and organ-at-risk (OAR) objectives. The potential benefit of SIRT followed by a SBRT was evaluated based on OAR dose and predicted toxicity compared to the independent SBRT treatment.
Main results:
Following SIRT, 14/20 patients had at least one predicted non-responding tumor considered eligible for a SBRT boost. When comparing SBRT plans, 10/14 (71%) SBRTboost and 12/20 (60%) SBRTalone plans were within OAR dose constraints. For three patients, SBRTboost plans were within OAR constraints while SBRTalone plans were not. Across the 14 eligible patients, SBRTboost plans had significantly less dose to the healthy liver (decrease in mean dose was on average ± standard deviation, 2.09 Gy ± 1.99 Gy, ) and reduced the overall targeted PTV volume (39% ± 21%) compared with SBRTalone.
Significance:
A clinical methodology for treating HCC using a synergized SIRT and SBRT approach is presented, demonstrating that it could reduce normal tissue toxicity risk in a majority of our retrospectively evaluated cases. Selectively targeting SIRT underdosed HCC lesions, or lesion subvolumes, with SBRT could improve tumor control and patient outcomes post-SIRT and allow SIRT to function as a target debulking tool for cases when SBRT is not independently feasible.
... These microspheres could facilitate real-time dose-delivery feedback and potentially obviate the need for PET-or SPECT-based microsphere visualization with continued use of 90 Y and its associated knowledge and infrastructure. Although studies (41)(42)(43) of these microspheres are currently limited to simulations and preclinical studies, a clinical trial is underway evaluating their safety and effectiveness in the treatment of patients with HCC and colorectal liver metastases. ...
Yttrium-90 transarterial radioembolization (TARE) has progressed from a salvage or palliative lobar or sequential bilobar regional liver therapy for patients with advanced disease to a versatile, potentially curative, and often highly selective local treatment for patients across Barcelona Clinic Liver Cancer stages. With this shift, radiation dosimetry has evolved to become more tailored to patients and target lesion(s), with treatment dose and distributions adapted for specific clinical goals (ie, palliation, bridging or downstaging to liver transplantation, converting to surgical resection candidacy, or ablative/curative intent). Data have confirmed that "personalizing" dosimetry yields real-world improvements in tumor response and overall survival while maintaining a favorable adverse event profile. In this review, imaging techniques used before, during, and after TARE have been reviewed. Historical algorithms and contemporary image-based dosimetry methods have been reviewed and compared. Finally, recent and upcoming developments in TARE methodologies and tools have been discussed.
... İtriyum-90 (Y90) radyoembolizasyonu 20 yıldan uzun süredir klinik uygulaması olan, primer ve metastatik karaciğer kanseri tedavisinde kullanılan bir tedavi yöntemidir [1]. Y90 radyoembolizasyonunda, radyoaktif mikro küreler hepatik arterden kateter ile giriş yapılarak karaciğerde bulunan tümör içine verilmektedir [2]. Saf βradyasyonu yayıcısı olan Y90, 2.67 günlük (64,1 saat) fiziksel yarılanma ömrüne sahip olup, yarılanma sonucu stabil zirkonyum-90 'a dönüşmektedir. ...
z: İtriyum-90 (Y90) radyoembolizasyonu primer ve metastatik karaciğer kanseri tedavisinde kullanılan bir yöntemdir. Tedavide, Y90 aktivite miktarının (MBq) hastaya spesifik dozimetri ile hesaplanması gerekmektedir. Her bir hasta için dozimetrinin yapılması oldukça uzun sürmektedir. Klinikteki işleyişi hızlandırmak, kanser hastalarına daha hızlı tedavi sağlamak ve ilgili personelin iş yükünü azaltarak efektif çalışma düzeni oluşturmak adına dozimetrinin yerini alabilecek bir alternatife ihtiyaç duyulmaktadır. Bu nedenle çalışmada, Y90 radyoembolizasyonu için hesaplanmış dozimetri sonuçları kullanılarak üç farklı makine öğrenmesi regresyon metodu modellenmesi sonucu Y90 terapötik aktivite miktarının tahmin edilmesi amaçlanmıştır. Tümör kütlesi (g), karaciğer kütlesi (g), tümör/karaciğer sayım oranı (%), şant oranı (%), tümör tutulumu ve karaciğer tutulumu gibi nümerik parametreler girdi olarak, Y90 aktivite miktarı (MBq) çıktı olarak belirlenmiştir. Çoklu doğrusal regresyon (MLR), rassal orman regresyonu (RF) ve destek vektör regresyonu (SVM) kullanılarak tahminler gerçekleştirilmiştir. Tahmin yöntemlerinin performanslarını değerlendirmede ortalama mutlak yüzde hatası (MAPE), ortalama mutlak hata (MAE), ortalama karekök sapması (RMSE), ortalama karesel hata (MSE) ve doğruluk (%) ölçütleri kullanılarak optimal tahmin modeli belirlenmeye çalışılmıştır. Anahtar kelimeler: Makine öğrenmesi, itriyum-90, çoklu lineer regresyon, rassal orman regresyon, destek vektör regresyonu. Activity Prediction with Machine Learning in Y90 Radioembolization Therapy Abstract: Yttrium-90 (Y90) radioembolization is a method used in the treatment of primary and metastatic liver cancer. In treatment, the amount of Y90 activity (MBq) should be calculated by patient-specific dosimetry. Dosimetry takes a long time to perform for each patient. There is a need for an alternative that can replace dosimetry to speed up the functioning of the clinic, provide faster treatment to cancer patients, and create an effective working order by reducing the workload of the relevant personnel. Therefore, the aim of this study was to estimate amount of Y90 therapeutic activity by modeling three different machine learning regression methods using calculated dosimetry results for Y90 radioembolization. Numerical parameters such as tumor mass (g), liver mass (g), tumor/liver count ratio (%), shunt rate (%), tumor involvement, and liver involvement were determined as input, and Y90 activity amount (MBq) was determined as output. Estimates were made using multiple linear regression (MLR), random forest regression (RF), and support vector regression (SVM). In evaluating the performance of estimation methods, the optimal estimation model was tried to be determined by using the mean absolute percent error (MAPE), mean absolute error (MAE), root mean square deviation (RMSE), mean square error (MSE) and accuracy (%).
... İtriyum-90 (Y90) radyoembolizasyonu 20 yıldan uzun süredir klinik uygulaması olan, primer ve metastatik karaciğer kanseri tedavisinde kullanılan bir tedavi yöntemidir [1]. Y90 radyoembolizasyonunda, radyoaktif mikro küreler hepatik arterden kateter ile giriş yapılarak karaciğerde bulunan tümör içine verilmektedir [2]. Saf βradyasyonu yayıcısı olan Y90, 2.67 günlük (64,1 saat) fiziksel yarılanma ömrüne sahip olup, yarılanma sonucu stabil zirkonyum-90 'a dönüşmektedir. ...
İtriyum-90 (Y90) radyoembolizasyonu primer ve metastatik karaciğer kanseri tedavisinde kullanılan bir yöntemdir. Tedavide, Y90 aktivite miktarının (MBq) hastaya spesifik dozimetri ile hesaplanması gerekmektedir. Her bir hasta için dozimetrinin yapılması oldukça uzun sürmektedir. Klinikteki işleyişi hızlandırmak, kanser hastalarına daha hızlı tedavi sağlamak ve ilgili personelin iş yükünü azaltarak efektif çalışma düzeni oluşturmak adına dozimetrinin yerini alabilecek bir alternatife ihtiyaç duyulmaktadır. Bu nedenle çalışmada, Y90 radyoembolizasyonu için hesaplanmış dozimetri sonuçları kullanılarak üç farklı makine öğrenmesi regresyon metodu modellenmesi sonucu Y90 terapötik aktivite miktarının tahmin edilmesi amaçlanmıştır. Tümör kütlesi (g), karaciğer kütlesi (g), tümör / karaciğer sayım oranı (%), şant oranı (%), tümör tutulumu ve karaciğer tutulumu gibi nümerik parametreler girdi olarak, Y90 aktivite miktarı (MBq) çıktı olarak belirlenmiştir. Çoklu doğrusal regresyon (ÇDR), rassal orman regresyonu (ROR) ve destek vektör regresyonu (SVM) kullanılarak tahminler gerçekleştirilmiştir. Tahmin yöntemlerinin performanslarını değerlendirmede ortalama mutlak yüzde hatası (MAPE), ortalama mutlak hata (MAE), ortalama karekök sapması (RMSE), ortalama karesel hata (MSE) ve doğruluk (%) ölçütleri kullanılarak optimal tahmin modeli belirlenmeye çalışılmıştır.
... More recently, Daniel Boyd's team at Dalhousie University, Canada, has developed a new radioactive glass that activates radioembolization and shows potential in treating cancer. This material, trademarked as Eye90 Microsphere™ glass, is being commercialized by ABK Biomedical Co. [165][166][167]. To learn more about radiopaque BGs for targeting cancer, interested readers can refer to a recent review by Moeini et al. [168]. ...
... More recently, Daniel Boyd's team at Dalhousie University, Canada, has developed a new radioactive glass that activates radioembolization and shows potential in treating cancer. This material, trademarked as Eye90 Microsphere TM glass, is being commercialized by ABK Biomedical Co. [165][166][167]. To learn more about radiopaque BGs for targeting cancer, interested readers can refer to a recent review by Moeini et al. [168]. ...
Radiopacity is sometimes an essential characteristic of biomaterials that can help clinicians perform follow-ups during pre- and post-interventional radiological imaging. Due to their chemical composition and structure, most bioceramics are inherently radiopaque but can still be doped/mixed with radiopacifiers to increase their visualization during or after medical procedures. The radiopacifiers are frequently heavy elements of the periodic table, such as Bi, Zr, Sr, Ba, Ta, Zn, Y, etc., or their relevant compounds that can confer enhanced radiopacity. Radiopaque bioceramics are also intriguing additives for biopolymers and hybrids, which are extensively researched and developed nowadays for various biomedical setups. The present work aims to provide an overview of radiopaque bioceramics, specifically crystalline, non-crystalline (glassy), and nanostructured bioceramics designed for applications in orthopedics, dentistry, and cancer therapy. Furthermore, the modification of the chemical, physical, and biological properties of parent ceramics/biopolymers due to the addition of radiopacifiers is critically discussed. We also point out future research lacunas in this exciting field that bioceramists can explore further
... 46 More recently, Daniel Boyd's team at Dalhousie University, Canada, has developed another radioactive glass that triggers radioembolization and shows promise for treating cancer. This product, trade named Eye90 Microsphere glass, is being commercialized by ABK Biomedical Co. [47][48][49] Recently, it was observed that TheraSphere-based therapy combined with chemotherapy had advantageous effects in selected patients with metastatic colorectal liver cancer. Still, even patients with the chemotherapy-resistant disease received some benefits from the treatment. ...
There is an ongoing profound shift in using glass as a primarily passive material to one that instills active properties. We believe and demonstrate that bioactive glasses (BGs) and glass–ceramics (BGCs) as functional biomaterials for cancer therapy can transform the world of healthcare in the 21st century. Melt/gel‐derived BGs and BGCs can carry many exotic elements, including less common rare‐earth, and trigger highly efficient anticancer properties via the combination of radiotherapy, photothermal therapy, magnetic hyperthermia, along with drug or therapeutic ions delivery. The addition of these dopants modifies the bioactivity, imparts novel functionalities, and induces specific biological effects that are not achievable using other classes of biomaterials. In this paper, we have briefly reviewed and discussed the current knowledge on promising compositions, processing parameters, and applications of BGs and BGCs in treating cancer. We also envisage the need for further research on this particular, unique class of BGs and BGCs.
... Preclinical dosimetry studies using small animals are an indispensable step in the pathway from in vitro experiments to clinical implementation of new radioisotope therapies. A lot of studies have shown the practicality of using animal distribution as a model for estimating the absorbed dose in humans [121][122][123][124][125]. ...
The article presents the problems of clinical implementation of personalized radioisotope therapy. The use of radioactive drugs in the treatment of malignant and benign diseases is rapidly expanding. Currently, in the majority of nuclear medicine departments worldwide, patients receive standard activities of therapeutic radiopharmaceuticals. Intensively conducted clinical trials constantly provide more evidence of a close relationship between the dose of radiopharmaceutical absorbed in pathological tissues and the therapeutic effect of radioisotope therapy. Due to the lack of individual internal dosimetry (based on the quantitative analysis of a series of diagnostic images) before or during the treatment, only a small fraction of patients receives optimal radioactivity. The vast majority of patients receive too-low doses of ionizing radiation to the target tissues. This conservative approach provides "radiation safety" to healthy tissues, but also delivers lower radiopharmaceutical activity to the neoplastic tissue, resulting in a low level of response and a higher relapse rate. The article presents information on the currently used radionuclides in individual radioisotope therapies and on radionuclides newly introduced to the therapeutic market. It discusses the causes of difficulties with the implementation of individualized radioisotope therapies as well as possible changes in the current clinical situation.
... Additionally, different types of 166 Ho microspheres with a higher density have been developed, which would increase the CT quantification capabilities [29,30]. 90 Y-based microspheres used for TARE can be visualized by SPECT [31] and PET [32], and in a recent publication, the CT-based quantification of a novel radiopaque 90 Y microsphere was investigated in a preclinical model [33]. In general, nuclear medicine imaging modalities have much longer acquisition times than CT or MRI, making them less favourable for image guidance during TARE. ...
Purpose
Transarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 ( ¹⁶⁶ Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing ¹⁶⁶ Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry.
Methods
Six patients were treated with ¹⁶⁶ Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, ¹⁶⁶ Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for ¹⁶⁶ Ho TARE.
Results
Administration of ¹⁶⁶ Ho microspheres within the MRI scanner was feasible in 9/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18/19 (95%) of treated tumours. Two CTCAE grade 3–4 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4/18 tumours exhibited signs of saturation, while in 14/18 tumours, the microsphere uptake patterns did not deviate from the linear trend.
Conclusion
This study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization.
Registration
Clinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered).
