Development of injectable fiducial markers for image guided radiotherapy with dual MRI and CT visibility

A composition for at least MR imaging, comprising non-water soluble carbohydrates, wherein at least 50% of the non-water soluble carbohydrates are carbohydrates selected from derivatives of lactose, maltose, trehalose, raffinose, glucosamine, galactosamine, lactosamine, sucrose or derivatives of sucrose, or mixed saccharides, or derivatives of disaccharides with at least two pyranose saccharide units, trisaccharides, tetrasaccharides, or mixtures thereof, and wherein the composition is a liquid before administration into the human or animal body and increases in viscosity by more than 1,000 centipoise (cP) after administration, wherein the composition contains at least one imaging contrast agent, and wherein the composition provides a phase separation which provides a clear contrast distinction in MR imaging, wherein the clear contrast distinction is bright vs dark in two different phases of the composition after administration into the human or animal body, and wherein the bright or dark phase is provided by said non-water soluble carbohydrates,

• wherein the disaccharides have structures selected from:
• wherein R1, R2, R3, R4, R5, R6, R7, and R8 in formulae I, II and III are selected collectively from the group consisting of hydrogen, alkanoyl, hydroxyl-substituted alkanoyl, and acyloxy-substituted alkanoyl, alkanyl, hydroxysubstituted alkanyl and acyloxy substituted alkanyl;
• or wherein R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting of hydrogen, alkanoyl, hydroxyl-substituted alkanoyl, and acyloxy-substituted alkanoyl, alkanyl, hydroxysubstituted alkanyl and acyloxy substituted alkanyl;
• or wherein all groups of R1, R2, R3, R4, R5, R6, R7, and R8 are selected collectively from the group consisting of acetyl, isobutyryl or propionyl;
• or wherein R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting acetyl, isobutyryl or propionyl;
• and further comprising pure anomers or mixtures of α- and β-anomers of structural Formulae of I, II, III,
• wherein the composition contains an MR imaging contrast agent containing at least one of gadolinium associated with a chelate chosen from PLA-DTPA or PLA-DOTA polymer chelates, or gadolinium-chelating lipids with DOPE-DOTA(Gd) or BSA-DTPA.