HoAcAc Microspheres: In Vitro and In Vivo Stability Studies Table I Elemental Composition of the HoAcAcMS after Incubation in a 116 mM Phosphate Buffer C H O Ho P Compositiond Day 0a %b noc 26.4 7.5 4.0 13.5 20.3 4.3 48.4 1.0 0.5 0.05 Ho2(AcAc)3 * H2O Day 1 % no 15.0 4.4 3.5 12.0 29.0 6.3 47.2 1.0 5.2 0.6 Intermediate Day 4 % 1.0 0.3 1.5 4.9 35.4 7.2 50.8 1.0 10.7 1.1 HoPO4 * 3 H2O Day 7 % 0.6 0.2 2.2 7.5 37.9 8.1 48.2 1.0 10.7 1.2 HoPO4 * 3 H2O Day 30 % no 0.5 0.1 1.5 4.5 30.9 5.7 55.5 1.0 11.3 1.1 HoPO4 * 3 H2O no no 831 no Day 90 % 0.7 0.2 1.6 4.6 30.1 5.6 55.8 1.0 11.0 1.0 HoPO4 * 3 H2O a data taken from Bult et al. (12) b results from elemental analysis are the mean of two values c no: the number of atoms, normalized on holmium d Composition: the chemical composition of the particles 50 mg mL−1 (=500 MBq 166HoAcAcMS mL−1). The microspheres were suspended by gentle agitation and repeatedly drawing them up and down with a syringe. Subsequently, approximately 200 μL (=100 MBq or 10 mg 166HoAcAcMS) was taken up in 29 G insulin syringes (Becton Dickinson Ultra Fine, Breda, the Netherlands), and the activity was measured using a dose calibrator (VDC-404, Veenstra Instruments, Joure, The Netherlands). As a control, a suspension of non-radioactive microspheres was prepared in a similar concentration of microspheres (50 mg mL−1). Approximately 200 μL (or 10 mg) was taken up in 29 G insulin syringes. Administration of 166HoAcAcMS Fourteen days post implantation the tumor reached a size of approximately 2 cm3 and a second subxiphoid laparotomy was performed. Prior to administration of the microspheres, the syringe was agitated vigorously to obtain a homogeneous microsphere suspension. One hundred μl of non-radioactive (=5 mg) or radioactive HoAcAcMS (=50 MBq, which corresponds to 5 mg) suspension was administered intratumorally. The syringes were measured in a dose calibrator before and after administration, to determine the injected amount of activity. Following the intratumoral administration of 166HoAcAcMS, the animals were subjected to planar gamma scintigraphy (Forte, Philips Medical Systems, Best, The Netherlands) and CT imaging (Brilliance 64, Philips Medical Systems, Best, The Netherlands) to confirm the selective deposition of microspheres in the tumor. Release Profile of the 166HoAcAcMS The urine and faeces of the animals were collected at the same time each day during the first week after Fig. 3 TOF-SIMS spectra from control HoAcAcMS (HoAcAcMS) and buffer incubated HoAcAcMS (HoAcAcMS buffer). The micrographs show total ion count images in the negative (−ve) and the positive (+ve) secondary ion mode. The peaks of interest are indicated with an arrow.