Production of GMP-grade radioactive holmium loaded poly(l-lactic acid) microspheres for clinical application

Zielhuis, S.W.; Nijsen, J. Frank W.; Roos, Remmert de; Krijger, Gerard C.; Rijk, Peter P. van; Hennink, Wim E.; Schip, Alfred D. van het

doi:10.1016/j.ijpharm.2005.12.034

Cited by 50 publications

(32 citation statements)

References 16 publications

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“…The Ho content, as measured by ICP, was 28 ± 3% w: w, which is superior to the value of 17 ± 0.5% obtained by the Ho-loaded poly(Llactic acid) microspheres produced by the University Medical Center (Utrecht, Netherlands) [10]. This value will potentially enable the delivery of a high radioactive dose to tumor cells.…”

Section: Resultsmentioning

confidence: 71%

“…Similarly, holmium-166 poly(L-lactic acid) (¹⁶⁶Ho-PLLA) microspheres have been developed at University Medical Center Utrecht (Utrecht, Netherlands) for quantitative multimodal in vivo imaging [10]. Other types of microparticles composed of lowerdensity polymers, including alginate [11] and chitosan [12] containing 166 Ho, as well as nanosized carrier materials containing stable 165 Ho for subsequent neutron activation [13], have also been reported.…”

Section: Animal and Surgical Proceduresmentioning

confidence: 99%

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Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

Marcon¹,

Géhan²,

Khoshnevis³

et al. 2017

J Nanomed Nanotechnol

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Section: Resultsmentioning

confidence: 71%

Section: Animal and Surgical Proceduresmentioning

confidence: 99%

Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

Marcon¹,

Géhan²,

Khoshnevis³

et al. 2017

J Nanomed Nanotechnol

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“…The Utrecht group have successfully produced poly (L-lactic acid) microspheres loaded with holmium-166 ( 166 Ho-PLLA) [133], and proposed a phase 1 trial (called HEPAR) to treat patients with liver metastases in 2010 [134], with a dose-escalation protocol of 20, 40, 60 and 80 Gy using MIRD macrodosimetry (achieved with varying GBq/kg of liver weight). The properties of the microspheres are shown in Table 3.…”

Section: Other Treatment Isotopesmentioning

confidence: 99%

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

Doherty¹

2015

J Diagn Imaging Ther

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Yttrium-90 radioembolization ( 90 Y-RE) is a well-established therapy for the treatment of hepatocellular carcinoma (HCC) and also of metastatic liver deposits from other malignancies. Nuclear Medicine and Cath Lab diagnostic imaging takes a pivotal role in the success of the treatment, and in order to fully exploit the efficacy of the technique and provide reliable quantitative dosimetry that are related to clinical endpoints in the era of personalized medicine, technical challenges in imaging need to be overcome. In this paper, the extensive literature of current 90 Y-RE techniques and challenges facing it in terms of quantification and dosimetry are reviewed, with a focus on the current generation of 3D dosimetry techniques. Finally, new emerging techniques are reviewed which seek to overcome these challenges, such as highresolution imaging, novel surgical procedures and the use of other radiopharmaceuticals for therapy and pre-therapeutic planning.

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“…Holmium-poly(L-lactic acid) microspheres with a mean diameter of 30 mm (range, 20-50 µm) were produced at the University Medical Center Utrecht in compliance with good manufacturing practice regulations, as described previously (12,13). The holmium, which was homogeneously incorporated into these microspheres (18.7% w/w ratio), was applied as a radioactive isotope for tumor destruction using its b radiation (E bmax 5 1.77 MeV and E bmax 5 1.85 MeV; radiation yield per disintegration, 0.487 and 0.500, respectively; half-life, 26.8 h), as a radioactive isotope for SPECT imaging using its g radiation (E g 5 80.6 keV; radiation yield per disintegration, 0.067), and as a contrast agent for MR imaging.…”

Section: Microspheresmentioning

confidence: 99%

In Vivo Dosimetry Based on SPECT and MR Imaging of¹⁶⁶Ho-Microspheres for Treatment of Liver Malignancies

et al. 2013

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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 . The contours of all liver segments and all discernible tumors were manually delineated on T2-weighted posttreatment MR images and registered to the posttreatment SPECT images (n 5 9) or SPECT/CT images (n 5 6) and MR imagingbased R 2 * maps (n 5 14). Dosimetry was based on SPECT (n 5 15) and MR imaging (n 5 9) for all volumes of interest, tumor-tonontumor (T/N) activity concentration ratios were calculated, and correlation and agreement of MR imaging-and SPECT-based measurements were evaluated. Results: The median overall T/N ratio was 1.4 based on SPECT (range, 0.9-2.8) and 1.4 based on MR imaging (range, 1.1-3.1). In 6 of 15 patients (40%), all tumors had received an activity concentration equal to or higher than the normal liver (T/N ratio $ 1). Analysis of SPECT and MR imaging measurements for dose to liver segments yielded a high correlation (R 2 5 0.91) and a moderate agreement (mean bias, 3.7 Gy; 95% limits of agreement, 211.2 to 18.7). Conclusion: With the use of 166 Ho-microspheres, in vivo dosimetry is feasible on the basis of both SPECT and MR imaging, which enables personalized treatment by selective targeting of inadequately treated tumors. Radi oembolization is an interventional oncologic treatment during which radioactive microspheres are administered in the arterial vessels supplying the liver and its tumors. The rationale behind this intraarterial liver treatment is that liver tumors are predominantly supplied by arterial blood, in contrast to the nontumorous liver, which relies mainly on the portal vein for its blood supply. Injection of a substance into the hepatic artery will therefore selectively target the tumorous tissue (1). Currently, the commercially available microspheres that are used for radioembolization are labeled with 90 Y. To be able to quantitatively evaluate the optimal and selective distribution of microspheres to the liver tumors, posttreatment imaging is indispensable. For that reason, optimization of posttreatment imaging of 90 Y-microspheres with bremsstrahlung SPECT and PET has recently gained interest (2-5).166 Ho-poly(L-lactic acid) microspheres have been developed at our institute as an alternative to 90 Y-microspheres specifically to be able to visualize the in vivo biodistribution of microspheres after radioembolization. 166 Ho-microspheres can be imaged with both SPECT and MR imaging, using the emission of g-photon radiation and the paramagnetic properties of holmium, respectively (6-10). Exploiting these qualities, multimodal dosimetry becomes feasible,...

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Production of GMP-grade radioactive holmium loaded poly(l-lactic acid) microspheres for clinical application

Cited by 50 publications

References 16 publications

Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

In Vivo Dosimetry Based on SPECT and MR Imaging of¹⁶⁶Ho-Microspheres for Treatment of Liver Malignancies

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Production of GMP-grade radioactive holmium loaded poly(l-lactic acid) microspheres for clinical application

Cited by 50 publications

References 16 publications

Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

Synthesis of Highly-loaded Holmium-165 Siloxane Particles for Brachytherapy of Brain Cancer and Injectability Evaluation in Healthy Pig

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

In Vivo Dosimetry Based on SPECT and MR Imaging of166Ho-Microspheres for Treatment of Liver Malignancies

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In Vivo Dosimetry Based on SPECT and MR Imaging of¹⁶⁶Ho-Microspheres for Treatment of Liver Malignancies