Neodymium-140 DOTA-LM3: Evaluation of an Generator for PET with a Non-Internalizing Vector.

Nd ( = 3.4 days), owing to its short-lived positron emitting daughter Pr ( = 3.4 min), has promise as an generator for positron emission tomography (PET). However, the electron capture decay of Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an redistribution of the daughter Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled Pr affects preclinical imaging with Nd. To explore the effect, Nd was produced at CERN-ISOLDE, reacted with the somatostatin analogue, DOTA-LM3 (1,4,7,10- tetraazacyclododecane, 1,4,7- tri acetic acid, 10- acetamide N - p-Cl-Phecyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH2) and injected into H727 xenograft bearing mice. Comparative pre- and post-mortem PET imaging at 16 h postinjection was used to quantify the redistribution of Pr following Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of Nd-DOTA-LM3 (13% ID/g at 16 h) coupled with the largest observed redistribution rate, where 56 ± 7% ( = 4, mean ± SD) of the produced Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free Pr. Based upon these results, we conclude that Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free Pr. This redistribution phenomenon may show promise as a probe of the cellular interaction with the vector, such as in determining tissue dependent internalization behavior.