Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+

Peptide receptor- targeted radionuclide therapy is nowadays being performed with radiolabeled DOTA-conjugated peptides, such as [Y-90-DOTA(O),Tyr(3)] octreotide (also known as OctreoTher(R) or Y-90-DOTATOC). The incorporation of Y-90(3+) is typically greater than or equal to99%, however, since a total patient dose can be as high as 26 GBq or 700 mCi the amount of free Y-90(3+) (=non-DOTA- incorporated) can be substantial. Free Y-90(3+) accumulates in bone with undesired radiation of bone marrow as a consequence. Y-90-DTPA is excreted rapidly via the kidneys. Incorporation of free Y-90(3+) into 90Y-DTPA might prevent this fraction from being accumulated into bone, therefore we have investigated: the biodistribution in rats of (YCl3)-Y-90,, [Y-90-DOTA(0),Tyr(3)] octreotide, and Y-90-DTPA; possibilities to complex 10% of free Y-90(3+) in a [Y-90-DOTA(0),Tyr(3)]octreotide containing solution into Y-90-DTPA prior to intravenous injection; and effects of 10% free Y-90(3+) in [Y-90-DOTA(0),Tyr(3)]octreotide solution, in the presence and in the absence of excess DTPA, on the biodistribution of in rats. The following results are presented: (YCl3)-Y-90 showed high skeletal uptake (i.e., 1% ID (injected dose) per gram femur, with main localization in the epiphyseal plates) and a 24 h total body retention of 74% ID; 90Y-DTPA had rapid renal clearance, and 24 h total body retention of <5% ID: added free Y-90(3+) in [Y-90-DOTA(0),Tyr(3)] octreotide solution could rapidly be incorporated into Y-90-DTPA at room temperature; and accumulation of Y-90(3+) in femur, blood, and liver was related to the amount of free Y-90(3+), whereas these accumulations could be prevented by the addition of DTPA. In conclusion, the addition of excess DTPA to [Y-90-DOTA(0),Tyr(3)]octreotide with incomplete Y-90-incorporation is recommended. (C) 2004 Elsevier Inc. All rights reserved.