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Introduction: 68 Ga-radiopharmaceuticals are common in the field of Nuclear Medicine to visualize receptor-mediated processes. In contrast to straightforward labeling procedures for clinical applications, preclinical in vitro and in vivo applications are hampered for reasons like e.g. volume restriction, activity concentration, molar activity and osmolality. Therefore, we developed a semi-automatic system specifically to overcome these problems. A difficulty appeared unexpectedly, as intrinsic trace metals derived from eluate (Zn, Fe and Cu) are concentrated as well in amounts that influence radiochemical yield and thus lower molar activity., Methods: To purify Gallium-68 and to reduce the high elution volume of a 68 Ga-generator, a NaCl-based method using a column containing PS-H + was implemented in a low volume PEEK system. Influence on reducing osmolality, acidity and the amount of PS-H + resin (15-50 mg) was investigated. [ 68 Ga]Ga was desorbed from the PS-H + resin with acidified 2-5 M NaCl (containing 0.05 M of HCl) and 68 Ga-activity was collected. DOTA-TATE was used as a peptide model. All buffers and additives used for labeling were mixed with Chelex 100 (~1 g/50 mL) for >144 h and eventually filtered using a 0.22 μm filter (Millipore). Quantification of metals was performed after labeling by HPLC (UV)., Results: Gallium-68 activity could be desorbed from PS-H + cation column with 3 M NaCl, and >60% (120-180 MBq) of [ 68 Ga]Ga was collected in <0.3 mL. Taking into account the used amount of 68 Ga-eluate, buffer and other excipients, the overall amount of trace metal per labeling was <1.5 nmol. DOTA-TATE could be labeled with [ 68 Ga]Ga with high radiochemical yield, >99% (ITLC), and a radiochemical purity of >95% (HPLC)., Conclusion: With the here described concentration system and metal purification technique, a low activity containing 68 Ga-generator can be used to label DOTA-peptide in preclinical applicable amounts >60 MBq/nmol (40-60 MBq/0.1 mL) and within 20 min., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright 2004 Elsevier Inc.)