Development and validation of an innovative administration system to facilitate controlled holmium-166 microsphere administration during TARE.

Background: To develop and validate a novel administration device for holmium-166 transarterial radioembolisation (TARE) with the purpose of facilitating controlled fractional microsphere administration for a more flexible and image-guided TARE procedure.

Methods: A Controlled Administration Device (CAD) was developed using MR-conditional materials. The CAD contains a rotating syringe to keep the microspheres in suspension during administration.

Accuracy of holmium-166 SPECT/CT quantification over a large range of activities.

Background: Quantitative imaging is a crucial step for dosimetry in radionuclide therapies. Traditionally, SPECT/CT imaging is quantified based on scanner-specific conversion factors or self-calibration, but recently absolute quantification methods have been introduced in commercial SPECT reconstruction software (Broad Quantification, Siemens Healthineers). In this phantom study we investigate the accuracy of three quantification methods for holmium-166 SPECT/CT imaging, and provide recommendations for clinical dosimetry.

Adjuvant holmium-166 radioembolization after radiofrequency ablation in early-stage hepatocellular carcinoma patients: a dose-finding study (HORA EST HCC trial).

Purpose: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e.

Transarterial radioembolization: a systematic review on gaining control over the parameters that influence microsphere distribution.

Transarterial radioembolization (TARE) is an established treatment modality for patients with unresectable liver cancer. However, a better understanding of treatment parameters that influence microsphere distribution could further improve the therapy. This systematic review examines and summarizes the available evidence on intraprocedural parameters that influence the microsphere distribution during TARE as investigated by in vivo, ex vivo, in vitro and in silico studies.

Intratumoral injection therapies for locally advanced pancreatic cancer: systematic review.

Introduction: Pancreatic cancer has one of the worst prognoses of all cancers. Patients with locally advanced pancreatic cancer have a 12.7-20.

Intratumoral injection of holmium-166 microspheres as neoadjuvant therapy of soft tissue sarcomas in dogs.

Introduction: Minimally invasive microbrachytherapy is in development to treat solid tumors by intratumoral injection of (radioactive) holmium-166 (Ho) microspheres (MS). A high local dose can be administered with minimal damage to surrounding tissue because of the short soft tissue penetration depth of Ho beta radiation. We aimed to prospectively evaluate the safety and efficacy of Ho microbrachytherapy in client-owned canine patients with soft tissue sarcomas (STS).

Improving MRI-based dosimetry for holmium-166 transarterial radioembolization using a nonrigid image registration for voxelwise calculation.

Background: Transarterial radioembolization (TARE) is a treatment modality for liver tumors during which radioactive microspheres are injected into the hepatic arterial system. These microspheres distribute throughout the liver as a result of the blood flow until they are trapped in the arterioles because of their size. Holmium-166 ( Ho)-loaded microspheres used for TARE can be visualized and quantified with MRI, as holmium is a paramagnetic metal and locally increases the transverse relaxation rate .

Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery.

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.

Study Protocol: Adjuvant Holmium-166 Radioembolization After Radiofrequency Ablation in Early-Stage Hepatocellular Carcinoma Patients-A Dose-Finding Study (HORA EST HCC Trial).

Purpose: To investigate the biodistribution of holmium-166 microspheres (Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e.

Case Report: Radioactive Holmium-166 Microspheres for the Intratumoral Treatment of a Canine Pituitary Tumor.

In this case study, a client-owned dog with a large pituitary tumor was experimentally treated by intratumoral injection of radioactive holmium-166 microspheres (HoMS), named Ho microbrachytherapy. To our knowledge, this is the first intracranial intratumoral treatment through needle injection of radioactive microspheres. A 10-year-old Jack Russell Terrier was referred to the Clinic for Companion Animal Health (Faculty of Veterinary Medicine, Utrecht University, The Netherlands) with behavioral changes, restlessness, stiff gait, and compulsive circling.

Development of an MRI-Guided Approach to Selective Internal Radiation Therapy Using Holmium-166 Microspheres.

Selective internal radiation therapy (SIRT) is a treatment modality for liver tumours during which radioactive microspheres are injected into the hepatic arterial tree. Holmium-166 (Ho) microspheres used for SIRT can be visualized and quantified with MRI, potentially allowing for MRI guidance during SIRT. The purpose of this study was to investigate the MRI compatibility of two angiography catheters and a microcatheter typically used for SIRT, and to explore the detectability of Ho microspheres in a flow phantom using near real-time MRI.

Dedicated holmium microsphere administration device for MRI-guided interstitial brain microbrachytherapy.

Microbrachytherapy with radioactive holmium-166 (Ho) microspheres (MS) has the potential to be an effective treatment method for brain malignancies. Direct intratumoural delivery of Ho-MS and dose coverage of the whole tumour are crucial requirements. However, currently no dedicated instruments for controlled intratumoural delivery exist.

To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer.

Purpose: To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer.

Methods: A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded.

Quantitative dual-energy CT material decomposition of holmium microspheres: local concentration determination evaluated in phantoms and a rabbit tumor model.

Objectives: The purpose of this study was to assess the feasibility of dual-energy CT-based material decomposition using dual-X-ray spectra information to determine local concentrations of holmium microspheres in phantoms and in an animal model.

Materials And Methods: A spectral calibration phantom with a solution containing 10 mg/mL holmium and various tube settings was scanned using a third-generation dual-energy CT scanner to depict an energy-dependent and material-dependent enhancement vectors. A serial dilution of holmium (microspheres) was quantified by spectral material decomposition and compared with known holmium concentrations.

Characterization of holmium(iii)-acetylacetonate complexes derived from therapeutic microspheres by infrared ion spectroscopy.

Microspheres containing radioactive holmium-acetylacetonate are employed in emerging radionuclide therapies for the treatment of malignancies. At the molecular level, details on the coordination geometries of the Ho complexes are however elusive. Infrared ion spectroscopy (IRIS) was used to characterize several Ho-acetylacetonate complexes derived from non-radioactive microspheres.

Feasibility of CT quantification of intratumoural Ho-microspheres.

Background: Microspheres loaded with radioactive Ho (Ho-MS) are novel particles for radioembolisation and intratumoural treatment. Because of the limited penetration of β radiation, quantitative imaging of microsphere distribution is crucial for optimal intratumoural treatment. Computed tomography (CT) may provide high-resolution and fast imaging of the distribution of these microspheres, with lower costs and widespread availability in comparison with current standard single-photon emission tomography (SPECT) and magnetic resonance imaging.

Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy.

Microspheres with high specific activities of radionuclides are very interesting for internal radiotherapy treatments. This work focuses on the formulation and characterization of inorganic microspheres with a high content of holmium and therefore a high specific radioactivity of holmium-166. Two novel formulations of inorganic microspheres were obtained by dispersing solid holmium acetylacetonate microspheres (Ho(AcAc)-ms) in NaHPO or NaOH solutions followed by 2 h incubation at room temperature.

The various therapeutic applications of the medical isotope holmium-166: a narrative review.

Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it emits high-energy beta radiation which can be used for a therapeutic effect and gamma radiation which can be used for nuclear imaging purposes. Furthermore, holmium-165 can be visualized by MRI because of its paramagnetic properties and by CT because of its high density.

Radioactive holmium phosphate microspheres for cancer treatment.

The aim of this study was the development of radioactive holmium phosphate microspheres (HoPO-MS) with a high holmium content and that are stable in human serum for selective internal radiation therapy (SIRT) of liver cancer. To this end, holmium acetylacetonate microspheres (HoAcAc-MS) were prepared (34.2 ± 1.

Production of novel diagnostic radionuclides in small medical cyclotrons.

The global network of cyclotrons has expanded rapidly over the last decade. The bulk of its industrial potential is composed of small medical cyclotrons with a proton energy below 20 MeV for radionuclides production. This review focuses on the recent developments of novel medical radionuclides produced by cyclotrons in the energy range of 3 MeV to 20 MeV.

Intratumoral injection of radioactive holmium-166 microspheres in recurrent head and neck squamous cell carcinoma: preliminary results of first use.

Background: Limited treatment options exist for patients with locoregional recurrences of head and neck squamous cell carcinoma (HNSCC). In the palliative setting, a single session, minimally invasive, and relatively safe therapy is desirable. This case series illustrates the feasibility of a direct intratumoral injection of radioactive holmium-166 microspheres (HoMS) in patients as a palliative treatment for recurrent HNSCC.

Intratumoral treatment with radioactive beta-emitting microparticles: a systematic review.

Purpose: The purpose of this study was to review the role of radioactive microparticles (1-100 μm) for the treatment of solid tumors and provide a comprehensive overview of the feasibility, safety, and efficacy.

Methods: A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2017) by combining synonyms for the determinants "tumor," "injection," and "radionuclide." Data on injection technique, toxicity, tumor response, and survival were collected.

Efficacy of Radioembolization with Ho-Microspheres in Salvage Patients with Liver Metastases: A Phase 2 Study.

Radioembolization of liver malignancies with Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of Ho radioembolization. In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection.

Intratumoral injection of radioactive holmium ( Ho) microspheres for treatment of oral squamous cell carcinoma in cats.

Background & Aims: A "microbrachytherapy" was developed as treatment option for inoperable tumours by direct intratumoral injection of radioactive holmium-166 ( Ho) microspheres (MS). Ho emits β-radiation which potentially enables a high, ablative, radioactive-absorbed dose on the tumour tissue while sparing surrounding tissues.

Materials & Methods: Safety and efficacy of Ho microbrachytherapy were evaluated in a prospective cohort study of 13 cats with inoperable oral squamous cell carcinoma without evidence of distant metastasis.

Radioembolization dosimetry: the road ahead.

Methods for calculating the activity to be administered during yttrium-90 radioembolization (RE) are largely based on empirical toxicity and efficacy analyses, rather than dosimetry. At the same time, it is recognized that treatment planning based on proper dosimetry is of vital importance for the optimization of the results of RE. The heterogeneous and often clustered intrahepatic biodistribution of millions of point-source radioactive particles poses a challenge for dosimetry.