Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An In Vitro and In Vivo Stability Study

Abstract

PurposeThe clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted.MethodsHoAcAcMS, before and after neutron irradiation, were incubated in a phosphate buffer at 37°C for 6 months. The in vitro release of holmium in this buffer after 6 months was 0.5%. Elemental analysis, scanning electron microscopy, infrared spectroscopy and time of flight secondary ion mass spectrometry were performed on the HoAcAcMS.ResultsAfter 4 days in buffer the acetylacetonate ligands were replaced by phosphate, without altering the particle size and surface morphology. HoAcAcMS before and after neutron irradiation were administered intratumorally in VX2 tumor-bearing rabbits. No holmium was detected in the faeces, urine, femur and blood. Histological examination of the tumor revealed clusters of intact microspheres amidst necrotic tissue after 30 days.ConclusionHoAcAcMS are stable both in vitro and in vivo and are suitable for intratumoral radionuclide treatment.

Intratumoral Administration of Holmium-166 Acetylacetonate Microspheres: Antitumor Efficacy and Feasibility of Multimodality Imaging in Renal Cancer

“…First of all, toxicity studies should be performed in humans. The in vivo stability of the HoAcAcMS was assessed in a tumor bearing rabbit model, which showed the stability of the HoAcAcMS for up to one month, and no toxicity was observed [21]. Radioactive holmium poly(L-lactic acid) particles of 20–50 µm for intra-arterial application have been evaluated for biodistribution, efficacy and toxicity in rats, rabbits and pigs, and have shown their stability and safety [29], [34], a phase-I study of patients with liver metastases has recently been performed [35], [36].…”

“…The size of the HoAcAcMS used range from 10–15 µm. Earlier in vitro and in vivo stability studies conducted with these HoAcAcMS before and after neutron irradiation have been described in detail by Bult et al [21]. Briefly, in vitro release of holmium was assessed after incubation at 37°C in phosphate buffer for 24 hours up to 180 days showing <0.3% and <0.5% free holmium, respectively.…”

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

“…Furthermore, according to the results of previous studies on the biodegradable PLLA microspheres irradiated in a reactor, such as 186 Re‐PLLA and 166 Ho‐PLLA to radioembolization of liver tumors, neutron activation strongly decreased the average molecular weight of the microspheres. Also, the heat production from gamma radiation melted the microspheres, so the microspheres were becoming misshaped and conglomerates and also likely led to the appearance of pores on the microsphere surface.…”

“…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.…”

“…166 Ho‐PLLA and 186 Re‐PLLA have been investigated previously. These radiomicrospheres are produced by irradiation in a reactor.…”