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 [90Y-DOTA 0,Tyr3]octreotide (also known as OctreoTher® or 90Y-DOTATOC). The incorporation of 90Y3+ is typically ≥99%, however, since a total patient dose can be as high as 26 GBq or 700 mCi the amount of free 90Y3+ (=non-DOTA- incorporated) can be substantial. Free 90Y3+ accumulates in bone with undesired radiation of bone marrow as a consequence. 90Y-DTPA is excreted rapidly via the kidneys. Incorporation of free 90Y3+ into 90Y-DTPA might prevent this fraction from being accumulated into bone, therefore we have investigated: the biodistribution in rats of 90YCl3, [90Y- DOTA0,Tyr3]octreotide, and 90Y-DTPA; possibilities to complex 10% of free 90Y3+ in a [ 90Y-DOTA0,Tyr3]octreotide containing solution into 90Y-DTPA prior to intravenous injection; and effects of 10% free 90Y3+ in [90Y-DOTA0,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: 90YCl3 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 90Y 3+ in [90Y-DOTA0,Tyr3]octreotide solution could rapidly be incorporated into 90Y-DTPA at room temperature; and accumulation of 90Y3+ in femur, blood, and liver was related to the amount of free 90Y3+, whereas these accumulations could be prevented by the addition of DTPA. In conclusion, the addition of excess DTPA to [90Y-DOTA0,Tyr 3]octreotide with incomplete 90Y-incorporation is recommended.

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