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).

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.

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.

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.

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.

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.

Radiation emission from patients treated with holmium-166 radioembolization.

Purpose: To assess the radiation exposure to individuals coming from patients after treatment with holmium-166 ((166)Ho) microspheres.

Materials And Methods: Holmium-166 radioembolization (RE) with escalating whole-liver doses of 20 Gy, 40 Gy, 60 Gy, and 80 Gy was administered to 15 patients. Exposure rates (μSv/h) from patients were measured at 1.

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

Purpose: Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization.

Quantitative Monte Carlo-based holmium-166 SPECT reconstruction.

Purpose: Quantitative imaging of the radionuclide distribution is of increasing interest for microsphere radioembolization (RE) of liver malignancies, to aid treatment planning and dosimetry. For this purpose, holmium-166 ((166)Ho) microspheres have been developed, which can be visualized with a gamma camera. The objective of this work is to develop and evaluate a new reconstruction method for quantitative (166)Ho SPECT, including Monte Carlo-based modeling of photon contributions from the full energy spectrum.

In vivo dosimetry based on SPECT and MR imaging of 166Ho-microspheres for treatment of liver malignancies.

Unlabelled: (166)Ho-poly(l-lactic acid) microspheres allow for quantitative imaging with MR imaging or SPECT for microsphere biodistribution assessment after radioembolization. The purpose of this study was to evaluate SPECT- and MR imaging-based dosimetry in the first patients treated with (166)Ho radioembolization.

Methods: Fifteen patients with unresectable, chemorefractory liver metastases of any origin were enrolled in this phase 1 study and were treated with (166)Ho radioembolization according to a dose escalation protocol (20-80 Gy).

Clinical and laboratory toxicity after intra-arterial radioembolization with (90)y-microspheres for unresectable liver metastases.

Objective: To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization ((90)Y-RE).

Methods: Patients with liver metastases treated with (90)Y-RE, between February 1(st) 2009 and March 31(st) 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts.

99mTc-macroaggregated albumin poorly predicts the intrahepatic distribution of 90Y resin microspheres in hepatic radioembolization.

Unlabelled: In hepatic (90)Y radioembolization, pretreatment (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) nuclear imaging is used for lung shunt analysis, evaluation of extrahepatic deposition, and sometimes for treatment planning, using a partition model. A high level of agreement between pretreatment (99m)Tc-MAA distribution and final (90)Y-microsphere distribution is assumed. The aim of this study was to investigate the value of pretreatment (99m)Tc-MAA SPECT to predict intrahepatic posttreatment (90)Y-microsphere distribution.

MRI-based biodistribution assessment of holmium-166 poly(L-lactic acid) microspheres after radioembolisation.

Objectives: To demonstrate the feasibility of MRI-based assessment of the intrahepatic Ho-PLLA-MS biodistribution after radioembolisation in order to estimate the absorbed radiation dose.

Methods: Fifteen patients were treated with holmium-166 ((166)Ho) poly(L-lactic acid)-loaded microspheres (Ho-PLLA-MS, mean 484 mg; range 408-593 mg) in a phase I study. Multi-echo gradient-echo MR images were acquired from which R (2) maps were constructed.

Microbrachytherapy using holmium-166 acetylacetonate microspheres: a pilot study in a spontaneous cancer animal model.

Purpose: Holmium-166 acetylacetonate microspheres ((166)Ho-AcAc-MS) are proposed as an intratumoral radioablation device. This article presents a pilot study in housecats with unresectable liver cancer. Feasibility and tolerability of intratumoral administrations of (166)Ho-AcAc-MS was investigated.

Holmium-166 radioembolisation in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study.

Background: The efficacy of radioembolisation for the treatment of liver tumours depends on the selective distribution of radioactive microspheres to tumorous tissue. The distribution of holmium-166 ((166)Ho) poly(L-lactic acid) microspheres can be visualised in vivo by both single-photon-emission CT (SPECT) and MRI. In this phase 1 clinical trial, we aimed to assess the safety and the maximum tolerated radiation dose (MTRD) of (166)Ho-radioembolisation in patients with liver metastases.

Transendocardial cell injection is not superior to intracoronary infusion in a porcine model of ischaemic cardiomyopathy: a study on delivery efficiency.

Stem cell therapy is a new strategy for chronic ischaemic heart disease in patients. However, no consensus exists on the most optimal delivery strategy. This randomized study was designed to assess cell delivery efficiency of three clinically relevant strategies: intracoronary (IC) and transendocardial (TE) using electromechanical mapping guidance (NOGA) compared to surgical delivery in a chronic pig model of ischaemic cardiomyopathy.

Magnetic resonance imaging-based radiation-absorbed dose estimation of 166Ho microspheres in liver radioembolization.

Purpose: To investigate the potential of magnetic resonance imaging (MRI) for accurate assessment of the three-dimensional (166)Ho activity distribution to estimate radiation-absorbed dose distributions in (166)Ho-loaded poly (L-lactic acid) microsphere ((166)Ho-PLLA-MS) liver radioembolization.

Methods And Materials: MRI, computed tomography (CT), and single photon emission CT (SPECT) experiments were conducted on an anthropomorphic gel phantom with tumor-simulating gel samples and on an excised human tumor-bearing liver, both containing known amounts of (166)Ho-PLLA-MS. Three-dimensional radiation-absorbed dose distributions were estimated at the voxel level by convolving the (166)Ho activity distribution, derived from quantitative MRI data, with a (166)Ho dose point-kernel generated by MCNP (Monte Carlo N-Particle transport code) and from Medical Internal Radiation Dose Pamphlet 17.

Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization.

Background: Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry.

Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial.

Background: Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy.

FID sampling superior to spin-echo sampling for T2*-based quantification of holmium-loaded microspheres: theory and experiment.

This work demonstrates both theoretically and experimentally that multiple gradient-echo sampling of free induction decay (MGEFID) is superior to MGE sampling of spin echo (MGESE) for T2*-based quantification of holmium-loaded microspheres (HoMS). An interleaved sampling strategy was applied in great detail to characterize the MR signal behavior of FID and SE signals of gels and perfused rabbit livers containing HoMS in great detail. Diffusion sensitivity was demonstrated for MGESE sampling, resulting in non-exponential signal decay on both sides of the SE peak and in an underestimation of the HoMS concentration.

Radionuclide liver cancer therapies: from concept to current clinical status.

Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery.