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J. F.W. Nijsen

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3 records found

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

Journal article - M. de Vries, N. J.M. Klaassen, N. C. Morsink, S. A. van Nimwegen, J. F.W. Nijsen, J. F.W. Nijsen, J.J. van den Dobbelsteen

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

Radioactive holmium phosphate microspheres for cancer treatment

Journal article - A. Gil Arranja, A. Gil Arranja, A. Gil Arranja, A. Gil Arranja, W. E. Hennink, A.G. Denkova, A.G. Denkova, R.W.A. Hendrikx, J. F.W. Nijsen, J. F.W. Nijsen, J. F.W. Nijsen

The aim of this study was the development of radioactive holmium phosphate microspheres (HoPO4-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 (Ho ...

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

Journal article - A. Gil Arranja, A. Gil Arranja, A. Gil Arranja, W. E. Hennink, C. Chassagne, A.G. Denkova, A.G. Denkova, J. F.W. Nijsen

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 (Ho2(AcAc)3-ms) in NaH2PO4 or NaOH solutions followed by 2 h incubation at room temperature. By exchange of acetylacetonate with phosphate or hydroxyl ions, holmium phosphate microspheres (HoPO4-ms) and holmium hydroxide microspheres (Ho(OH)3-ms) were formed respectively. The inorganic microspheres had a significantly smaller diameter (28.5 ± 4.4 μm (HoPO4-ms) and 25.1 ± 3.5 μm (Ho(OH)3-ms)) than those of Ho2(AcAc)3-ms (32.6 ± 5.2 μm). The weight percentage of holmium-165 in the microspheres increased significantly from 47% (Ho2(AcAc)3-ms) to 55% (HoPO4-ms) and 73% (Ho(OH)3-ms). After preparation of both HoPO4-ms and Ho(OH)3-ms, the stable holmium-165 isotope was partly converted by neutron activation into radioactive holmium-166 to yield radioactive microspheres. High specific activities were achieved ranging from 21.7 to 59.9 MBq/mg (166HoPO4-ms) and from 28.8 to 79.9 MBq/mg (166Ho(OH)3-ms) depending on the neutron activation time. The structure of both microspheres was preserved up to neutron activations of 6 h in a thermal neutron flux of 4.72 × 1016 n m−2 s−1. After activation, both microspheres revealed excellent stability in administration fluids (saline and phosphate buffer) having less than 0.05% of holmium released after 72 h incubation. Finally, the hemocompatibility of these inorganic microspheres was evaluated and it was shown that the microspheres did cause neither hemolysis nor depletion or inhibition of the coagulation factors of the intrinsic blood coagulation pathway meaning that the microspheres have a good hemocompatibility. Overall, this work shows that radioactive inorganic microspheres with high specific activities of holmium-166 can be prepared which potentially can be used for internal radionuclide therapy.@en

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Intratumoral holmium microsphere injection in pancreatic cancer

Master thesis - C.Y. Willink, J. F.W. Nijsen, S.F.M. Jenniskens, J.J. van den Dobbelsteen, J. Harlaar

Introduction: Pancreatic adenocarcinoma holds one of the worst prognosis of all known malignancies. Local treatment options for patients with unresectable pancreatic cancer may increase tumor control and benefit patient survival. This study aimed to test the feasibility of a possible new treatment method utilizing intratumoral holmium microsphere injections. Method: In this study, non-radioactive holmium-165 poly(L-lactic acid) microspheres (165Ho-PLLA-MS, HoMS) were injected in pancreatic adenocarcinoma in an ex-vivo setting. Patients signed informed consent to donate their resected pancreas with tumor to this study after conventional pancreatectomy. HoMS were brought in a suspension of Pluronic and Saline (5 mg HoMS per milliliter suspension) and was homogenized using an intratumoral injection device for HoMS. Pre- and post-injection MRI and CT were analyzed for holmium distribution. Visual holmium artefacts on MRI were manually segmented for a volume estimation. Results: Three tissue samples of 9.4 ml, 5.6 ml, and 11.2 ml were injected with 4.95 ml, 2.3 ml, and 1.8 ml HoMS suspension, respectively. Pre-injection MRI was used for treatment planning. Two tissue samples were injected using the pre-injection MRI and tumor palpation. In the last-sample additional ultrasound-guidance was performed. Injections were performed with minor leakage or needle obstruction. MRI segmentation showed fractions of the holmium artefacts visual in or near the tumor increased per sample with 26%, 43% and 68%, for sample 1, 2 and 3, respectively. Holmium quantification was performed on sample 3 and gave a simulated mean tumor dose 6 Gy and a mean dose in the largest deposits of 33 Gy. Small deposits were most likely excluded from quantification because of a low resolution. HoMS were not visible on CT. This was most likely caused by automated scanning parameters and a low HoMS concentration. Conclusion: Preliminary results show that intratumoral injection of HoMS in pancreatic adenocarcinoma is feasible in an ex-vivo setting. Improvements regarding microsphere concentration, imaging and quantification may be investigated during the final three patients in this trial. Considering the already reached distribution and injection control, intratumoral holmium microsphere injection may soon benefit patients with unresectable pancreatic cancer.