Neutron activation of holmium poly(L-lactic acid) microspheres for hepatic arterial radioembolization: a validation study

Vente, M. A. D.; Nijsen, J. Frank W.; Roos, Remmert de; Steenbergen, Mies J. van; Kaaijk, C. N. J.; Koster-Ammerlaan, M. J. J.; Leege, P.F.A. de; Hennink, Wim E.; Schip, Alfred D. van het; Krijger, Gerard C.

doi:10.1007/s10544-009-9291-y

Cited by 37 publications

(36 citation statements)

References 23 publications

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“…Moreover, the 166 Ho x-ray attenuation coefficient is sufficiently high enough to be used as a contrast agent for visualization through CT (6). The greatest disadvantage of 166 Ho PLLA is the relatively short half-life of the tracer, meaning that each dose will require separate neutron irradiation and a short logistic timeline to get the dose from the reactor to the patient (8).…”

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confidence: 99%

Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Gates¹,

Esmail²,

Marshall³

et al. 2010

J Nucl Med

118

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Radioembolization with 90 Y microspheres represents a novel transarterial radiation treatment for liver tumors. The purpose of this pilot study was to evaluate the findings of postimplantation PET/CT of 90 Y glass microspheres. Methods: Three patients with hepatocellular carcinoma and 2 patients with liver metastases (1 neuroendocrine, 1 colorectal) underwent PET/CT after radioembolization. Four patients underwent imaging at 1 mo to assess response and confirm PET/CT findings; 1 patient underwent PET/CT at 4 d after 90 The tracer 90 Y is traditionally thought of as a pure b-emitter. Thus, current clinical practice involves determining the distribution of the microspheres through bremsstrahlung imaging combined with anatomic imaging via SPECT/CT (1). Because bremsstrahlung imaging is based on a SPECT acquisition that uses either a wide imaging window or multiple energy windows due to the continuum, the scattered photon cannot easily be distinguished from true photons. Consequently, bremsstrahlung imaging is not quantifiable, and thus accurate dose distribution cannot be obtained (2).In an effort to improve pretreatment evaluation and follow-up, microspheres containing radionuclides that emit both b-and g-radiations have been proposed, and treatment with microspheres includes the use of 166 Ho and 186 Re/ 188 Re. At the time of this article's publication, glass and poly (L-lactic acid) (PLLA) microspheres incorporating 186 Re/ 188 Re had not been tested in human subjects with liver tumors. However, 188 Re human serum albumin microspheres ( 188 Re-HSAM) have been tested in a small cohort of patients at a single institution (3). The maximum b-particle energy of 188 Re (2.12 MeV) is lower than that of 90 Y (2.28 MeV), thus necessitating 4-to 5-fold-higher activities to obtain an absorbed dose equivalent to that of 90 Y. Because the g-energy (155 keV) is comparable to other nuclear medicine imaging agents, 188 Re-HSAM seems to be a good candidate for radioembolization of liver tumors. However, no conclusive effects could be derived from the study performed by Liepe et al. because of the small cohort size and heterogeneity of the patients' primary disease (3). To properly evaluate the effect of radioembolization of hepatic malignancies with 188 Re-HSAM, more studies and a larger patient cohort are warranted.Another promising radionuclide proposed for radioembolization of hepatic tumors is 166 Ho (maximum energy of the b-particle, 1.77 [48.7%] and 1.85 [50.5%] MeV and energy of the g-ray, 81 keV [6.7%]). 166 Ho PLLA microspheres are currently being used in patients with hepatic malignancies under a phase I clinical trial (4,5). Similar to the 188 Re HSAM dosimetry, the absorbed radiation dose per activity of 166 Ho (8.7 mGy/MBq) is lower than that of 90 Y (28 mGy/MBq). As a result, with 166 Ho 3 times the radioactivity will be required for radioembolization to achieve a dosimetry equivalent to that of 90 Y. The greatest advantage of 166 Ho is that it represents a multimodality imaging agent (6). The paramagnetic pro...

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mentioning

confidence: 99%

Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Gates¹,

Esmail²,

Marshall³

et al. 2010

J Nucl Med

118

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“…The amount of microspheres (600 mg) was weighed, packed in high-density polyethylene vials (Posthumus Plastics, Beverwijk, The Netherlands) and sent to the nuclear reactor (Delft University of Technology, Delft, The Netherlands) for neutron activation [21]. The calculation of the amount of radioactivity was based on liver weight, conforming to the clinically used approach for TheraSphere®.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2012

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ObjectivesTo demonstrate the feasibility of MRI-based assessment of the intrahepatic Ho-PLLA-MS biodistribution after radioembolisation in order to estimate the absorbed radiation dose.MethodsFifteen patients were treated with holmium-166 (166Ho) 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 R2* maps were constructed. The amount of Ho-PLLA-MS in the liver was determined by using the relaxivity r2* of the Ho-PLLA-MS and compared with the administered amount. Quantitative single photon emission computed tomography (SPECT) was used for comparison with MRI regarding the whole liver absorbed radiation dose.ResultsR2* maps visualised the deposition of Ho-PLLA-MS with great detail. The mean total amount of Ho-PLLA-MS detected in the liver based on MRI was 431 mg (range 236–666 mg) or 89 ± 19 % of the delivered amount (correlation coefficient r = 0.7; P < 0.01). A good correlation was found between the whole liver mean absorbed radiation dose as assessed by MRI and SPECT (correlation coefficient r = 0.927; P < 0.001).ConclusionMRI-based dosimetry for holmium-166 radioembolisation is feasible. Biodistribution is visualised with great detail and quantitative measurements are possible.Key Points• Radioembolisation is increasingly used for treating unresectable primary or metastatic liver tumours.• MRI-based intrahepatic microsphere biodistribution assessment is feasible after holmium-166 radioembolisation.• MRI enables quantification of holmium-166 microspheres in liver in a short imaging time.• MRI can estimate the whole liver absorbed radiation dose following holmium-166 radioembolisation.

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“…For effective radioembolization, the radionuclide must be a short‐lived high energy beta emitter. 90 Y, 186 Re, 188 Re, and 166 Ho radioisotopes have been tested for radioembolization, but only 90 Y‐microspheres are currently in routine clinical use. 90 Y glass‐based Thera‐Sphere1 (Nordion, Canada) and 90 Y resin‐based SIR‐Spheres1 (SIRTex, Australia) microspheres are commercially available radioembolic agents for radioembolization of liver tumors.…”

Section: Introductionmentioning

confidence: 99%

Preparation and evaluation of ¹⁸⁸Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy

Jamre

Shamsaei

Erfani

et al. 2018

Labelled Comp Radiopharmac

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Radioembolization with radioactive microspheres has been an effective method for the treatment of liver lesions. The aim of this study was to prepare carrier-free Re loaded poly (L-lactic acid) (PLLA) microspheres through Re sulfide colloidal nanoparticles ( Re-SC nanoparticles). The formation of Re-SC nanoparticles was confirmed by ultraviolet-visible spectrophotometry. The labeling yield of Re-SC nanoparticles was verified using the RTLC method. Effects of synthesis parameters on morphology and size of prepared Re-sulfide colloidal-PLLA microspheres ( Re-SC-PLLA microspheres) were studied by scanning electron microscopy. In vitro stability of Re-SC-PLLA microspheres was investigated in normal saline at room temperature and in human serum at 37°C. In vivo distribution studies and gamma camera imaging were performed in healthy BALB/c mice. The microspheres could be prepared with sizes between 13 and 48 μm (modal value 29 μm) and radiolabeling efficiency>99%. After incubation, the microspheres were found stable in vitro up to 72 hours. The biodistribution after intravenous injection in healthy BALB/c mice showed high accumulation in lung as a first capture pathway organ for microsphere followed by great retention over 48 hours for these microspheres. These data show that Re-SC-PLLA microspheres are suitable candidate for clinical studies.

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Neutron activation of holmium poly(L-lactic acid) microspheres for hepatic arterial radioembolization: a validation study

Cited by 37 publications

References 23 publications

Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

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

Preparation and evaluation of ¹⁸⁸Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy

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Neutron activation of holmium poly(L-lactic acid) microspheres for hepatic arterial radioembolization: a validation study

Cited by 37 publications

References 23 publications

Internal Pair Production of 90Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Internal Pair Production of 90Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

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

Preparation and evaluation of 188Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy

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Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Internal Pair Production of ⁹⁰Y Permits Hepatic Localization of Microspheres Using Routine PET: Proof of Concept

Preparation and evaluation of ¹⁸⁸Re sulfide colloidal nanoparticles loaded biodegradable poly (L‐lactic acid) microspheres for radioembolization therapy