Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

Abstract

Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-microm poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was < or =0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little 166Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6. 1+/-2.9 for rats with tumour (n=15) versus 0.7+/-0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma.

Monodisperse polymeric particles prepared by ink-jet printing: Double emulsions, hydrogels and polymer mixtures

“…In addition, specific applications such as embolization treatments to locally irradiate liver tumors or arrest the blood supply to uterine fibroids, depend critically on the size. For such applications manufacturing methods that yield high amounts of monodisperse particles are needed [9].…”

Neutron Activation Preparation of 166Ho-Albumin Microspheres as a Promising Radiopharmaceutical for Tumor Therapy

“…Microspheres of poly-L-lactic acid labeled with 166 Ho can be obtained by incorporation of stable 165 Ho in the particles and by subsequent irradiation with thermal neutrons [6,10]. However, these particles are unstable to irradiation with thermal neutrons at high fluxes [11], and choosing the optimal irradiation conditions for preparing poly-L-lactic acid microspheres labeled with 166 Ho is very difficult [6,12,13].…”

“…Microspheres of poly-L-lactic acid labeled with 166 Ho can be obtained by incorporation of stable 165 Ho in the particles and by subsequent irradiation with thermal neutrons [6,10]. However, these particles are unstable to irradiation with thermal neutrons at high fluxes [11], and choosing the optimal irradiation conditions for preparing poly-L-lactic acid microspheres labeled with 166 Ho is very difficult [6,12,13].The AMs labeled with 99m Tc were first prepared in 1969 [14], and at present it is the most widely used in nuclear medicine for diagnostics of lung diseases. As compared to the other materials for preparing microspheres, human albumin has several advantages: it is physiologically compatible, is easily metabolized in the living body, and actively binds various radionuclides.…”

Monitoring of Radionuclide Impurities in 166Ho-Albumin Microspheres Prepared by Neutron Activation with Thermal Neutrons

“…Labeled microspheres can be obtained by two procedures: (1) microspheres are first prepared and then labeled with 90 Y [4,6,8,9], 186 Re and 188 Re [1,7,9], or 166 Ho [5] and (2) stable isotopes are incorporated in the microspheres during their preparation and then activated with thermal neutrons in a reactor, forming microspheres labeled with 90 Y [11], 186 Re and 188 Re [16], 32 P [17], or 166 Ho [2,3].…”