Chemoradionuclide Therapy with¹⁸⁶Re-Labeled Liposomal Doxorubicin: Toxicity, Dosimetry, and Therapeutic Response

Abstract

This study was performed to determine the maximum tolerated dose (MTD) and therapeutic effects of rhenium-186 ( 186 Re)-labeled liposomal doxorubicin (Doxil), investigate associated toxicities, and calculate radiation absorbed dose in head and neck tumor xenografts and normal organs. Doxil and control polyethylene glycol (PEG)-liposomes were labeled using Re-Doxil has promising potential, because good tumor control was achieved with limited associated toxicity.

Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles

“…As described previously regarding image-guided RF ablation, studies with intravenously administered liposome nanoparticles containing both 186 Re and doxorubicin demonstrated an improved tumor response in a large solid tumor model in rats as compared to liposomes containing only doxorubicin [86,90,208]. A nanoparticle containing both 188 Re and doxorubicin for the intravenous treatment of a colon cancer model has also shown a synergistic tumor treatment efficacy of this combination [209].…”

“…The significantly increased RF ablation-induced uptake of liposomal doxorubicin within tumor tissue was also shown in a head and neck model using imaging with liposomal doxorubicin radiolabeled with 99m Tc or 186 Re [89,90]. These reports used a radiolabeling method for loading a commercial liposomal doxorubicin formulation with high activities of 99m Tc or 186 Re by taking advantage of the same pH gradient used to load doxorubicin into the liposomes [7].…”

“…Cancer therapy with these dual therapeutic carrier liposomes has been previously termed chemoradionuclide therapy [90]. When these dual therapeutic nanoparticles are combined with a third therapy of RF ablation, a further increased amount of tumor tissue can be effectively treated [86].…”

Radiopharmaceutical enhancement by drug delivery systems: A review

“…Another strategy includes the generation of a pH gradient with ammonium sulphate across the liposome interior (pH 5.1) and the liposome exterior (pH 7.4) [48]. Liposomes for nuclear medicine applications are mostly synthesised in a similar way [49][50][51][52][53][54][55][56]. Other methods includes adsorption or entrapment of the radiochemical to the liposome (with or without funtionalization of lipid component) with prolonged incubation [57][58][59][60][61] as well as the use of an ionophore (for example 2-hydroxyquinoline) to transport the radiochemical across the membrane [62].…”

Use of99mTc-doxorubicin scintigraphy in females with breast cancer: a pilot study

“…Labelling doxorubicin with radiopharmaceuticals may also be used to potentialize its effects. After an initial study evaluating the toxicity, dosimetry and therapeutic response of rhenium-186 ( Tc-doxorubicin scintigraphy in breast cancer BJR doxorubicin), 33 Soundararajan et al 34 further evaluated the therapeutic efficacy of 186 Re-liposomal doxorubicin combined with radiofrequency ablation of human head-and-neck squamous cell carcinoma xenograft in nude rats. Tumour uptake in 186 Re therapy groups was studied with small-animal SPECT for 5 days, and therapeutic efficacy was monitored for 6 weeks with measurement of tumour volume, calculation of the percentage injected dose of 18 F-FDG in tumour from small-animal PET images, and determination of viable tumour volume at histopathological examination.…”