Non-incorporated radionuclide post radiolabeling DOTA-peptides can effectively be complexed in vitro by addition of DTPA or EDTA

Objectives Radiolabeled DOTA-peptides are applied in Peptide Receptor Radionuclide Therapy or scintigraphy. Even if the incorporation of the radionuclide is almost 100%, there is always a fraction of non-incorporated remaining and in vivo will accumulate in bone and/or bone marrow with concordant unwanted radiation dose. The reported radiation dose in bone marrow for 67/68Ga, 90Y, 111In or 177Lu, are 0.11, 0.04, 3.3, 0.53 and 1.1 mGy.MBq-1, resp. Therefore, we investigated complexation of non-incorporated radioactivity by DTPA or EDTA on the biodistribution in rats.

Methods Rats were injected iv with DOTATOC or DOTA-tate, labeled with 68Ga, 90Y, 111In or 177Lu. Either labeled at 100% incorporation (A) or at an incomplete incorporation of 90%, thus 10% of remaining non-incorporated radionuclide was ionic (B). Parallel, rats were injected in which 10% remaining non-incorporated radionuclide was complexed by DTPA or EDTA (C) in vitro post radiolabeling and prior to administration. Control rats were injected with 68Ga, 90Y, 111In or 177Lu , either as chloride (D), or complexed with DTPA or EDTA (E).

Results Complete formation of 90Y-, 111In-, and 177Lu-DTPA in vitro was rapid (<15 min), in contrast to 68Ga-DTPA. Complete formation of 68Ga-EDTA was rapid (<15 min). Rats injected with 90% incorporation (B) showed higher retention of activity in blood, high accumulation in liver and skeleton, while this could be prevented by the in vitro addition of DTPA or EDTA (C). All 4 radionuclides, injected as chloride (D) showed high accumulation in skeleton and liver, and slow blood clearance. These values could strongly be reduced by the in vitro addition of DTPA or EDTA, and concordant rapid high renal clearance and low total body retention (E).

Conclusions Non-incorporated fraction of radionuclide in radiolabeled DOTA-peptides can efficiently be complexed in vitro by addition of DTPA or EDTA and effectively lowers unwanted radiation dose. In vitro addition of DTPA or EDTA is therefore strongly recommended.