title: Reduction of skeletal accumulation of radioactivity by co-injection of DTPA in [90Y-DOTA0,Tyr3]octreotide solutions containing free 90Y3+.
abstract: Peptide receptor-targeted radionuclide therapy is nowadays being performed with radiolabeled DOTA-conjugated peptides, such as [90Y-DOTA0,Tyr3]octreotide (also known as OctreoTher or 90Y-DOTATOC). The incorporation of 90Y3+ is typically > or = 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,Tyr3]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 90Y3+ 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,Tyr3]octreotide with incomplete 90Y-incorporation is recommended.
authors.affiliation: Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam, The Netherlands. w.a.p.breeman@erasmusmc.nl
authors.forename: Wouter A P
authors.initials: WA
authors.lastname: Breeman
authors.forename: Maarten Th M
authors.initials: MT
authors.lastname: De Jong
authors.forename: Erik
authors.initials: E
authors.lastname: De Blois
authors.forename: Bert F
authors.initials: BF
authors.lastname: Bernard
authors.forename: Marion
authors.initials: M
authors.lastname: De Jong
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000818:Animals; D001345:Autoradiography; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology*; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004369:Pentetic Acid / Q000494:pharmacology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D011917:Rats, Inbred Lew; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C121107:octreotide, DOTA-Tyr(3)-; D004369:Pentetic Acid; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide