OBJECTIVES: To study the effect of co-injecting unlabelled hypericin (Hyp) on biodistribution, necrosis uptake and tumour retention of iodine-123 or iodine-131 labelled hypericin ((123/131)I-Hyp), a necrosis avid agent for an anticancer radiotherapy. METHODS: (123/131)I-Hyp was prepared with Iodogen as oxidant and formulated in 0.6 μg/kg no-carrier-added (NCA) or 0.25 mg/kg unlabelled Hyp carrier-added (CA) forms using dimethyl sulfoxide/polyethylene glycol-400/propylene glycol/water (25/25/25/25% v/v/v/v), as solvent mixture. Comparisons on biodistribution and necrosis uptake of NCA and CA(123)I-Hyp were conducted on rats (n=24) of reperfused liver infarction (RPLI) in 48h p.i. Tumour retention of CA(131)I-Hyp was assessed in severe combined immunodeficiency (SCID) mice with fibrosarcoma (RIF-1) tumours (n=25) over 40 days. To cause intratumour necrosis, mice were pre-treated with a vascular disrupting agent CA4P at 10mg/kg. Tissue-gamma counting (TGC), autoradiography and histology were performed. RESULTS: TGC revealed no significant difference in organ biodistribution between RPLI-rats injected with NCA and CA(123)I-Hyp, except in intestines, liver, lungs and stomach (P<0.05). Both preparations showed hepatobiliary excretion since intestines and faeces retained the most radioactivity. NCA and CA(123)I-Hyp exhibited high avidity and selectivity for hepatic infarction. From the day after injection onward, CA(123)I-Hyp showed greater target accumulation (7-11%ID/g) than (123)I-Hyp alone (~4%ID/g; P<0.05). In RIF-1-SCID mice receiving CA(131)I-Hyp, prolonged high retention in tumour necrosis was detected over 40 days p. i. TGC findings were confirmed by histological and autoradiographic analysis. CONCLUSIONS: The study demonstrated the co-injection of unlabelled Hyp affected necrosis uptake but almost no biodistribution of radioiodinated Hyp. Long-term high retention into tumour necrosis characterizes the carrier-added (131)I-Hyp.
OBJECTIVES: To study the effect of co-injecting unlabelled hypericin (Hyp) on biodistribution, necrosis uptake and tumour retention of iodine-123 or iodine-131 labelled hypericin ((123/131)I-Hyp), a necrosis avid agent for an anticancer radiotherapy. METHODS: (123/131)I-Hyp was prepared with Iodogen as oxidant and formulated in 0.6 μg/kg no-carrier-added (NCA) or 0.25 mg/kg unlabelled Hyp carrier-added (CA) forms using dimethyl sulfoxide/polyethylene glycol-400/propylene glycol/water (25/25/25/25% v/v/v/v), as solvent mixture. Comparisons on biodistribution and necrosis uptake of NCA and CA(123)I-Hyp were conducted on rats (n=24) of reperfused liver infarction (RPLI) in 48h p.i. Tumour retention of CA(131)I-Hyp was assessed in severe combined immunodeficiency (SCID) mice with fibrosarcoma (RIF-1) tumours (n=25) over 40 days. To cause intratumour necrosis, mice were pre-treated with a vascular disrupting agent CA4P at 10mg/kg. Tissue-gamma counting (TGC), autoradiography and histology were performed. RESULTS: TGC revealed no significant difference in organ biodistribution between RPLI-rats injected with NCA and CA(123)I-Hyp, except in intestines, liver, lungs and stomach (P<0.05). Both preparations showed hepatobiliary excretion since intestines and faeces retained the most radioactivity. NCA and CA(123)I-Hyp exhibited high avidity and selectivity for hepatic infarction. From the day after injection onward, CA(123)I-Hyp showed greater target accumulation (7-11%ID/g) than (123)I-Hyp alone (~4%ID/g; P<0.05). In RIF-1-SCIDmice receiving CA(131)I-Hyp, prolonged high retention in tumour necrosis was detected over 40 days p. i. TGC findings were confirmed by histological and autoradiographic analysis. CONCLUSIONS: The study demonstrated the co-injection of unlabelled Hyp affected necrosis uptake but almost no biodistribution of radioiodinated Hyp. Long-term high retention into tumour necrosis characterizes the carrier-added (131)I-Hyp.
Authors: Marieke A Stammes; Vicky T Knol-Blankevoort; Luis J Cruz; Hans R I J Feitsma; Laura Mezzanotte; Robert A Cordfunke; Riccardo Sinisi; Elena A Dubikovskaya; Azusa Maeda; Ralph S DaCosta; Katja Bierau; Alan Chan; Eric L Kaijzel; Thomas J A Snoeks; Ermond R van Beek; Clemens W G M Löwik Journal: Mol Imaging Biol Date: 2016-12 Impact factor: 3.488
Authors: Marieke A Stammes; Azusa Maeda; Jiachuan Bu; Deborah A Scollard; Iris Kulbatski; Philip J Medeiros; Riccardo Sinisi; Elena A Dubikovskaya; Thomas J A Snoeks; Ermond R van Beek; Alan B Chan; Clemens W G M Löwik; Ralph S DaCosta Journal: Front Oncol Date: 2016-10-21 Impact factor: 6.244