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

(140)Nd (t(1/2) = 3.4 days), owing to its short-lived positron emitting daughter (140)Pr (t(1/2) = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of (140)Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter (140)Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled (140)Pr affects preclinical imaging with (140)Nd. To explore the effect, (140)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 in vivo redistribution of (140)Pr following (140)Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of (140)Nd-DOTA-LM3 (13% ID/g at 16 h) coupled with the largest observed redistribution rate, where 56 ± 7% (n = 4, mean ± SD) of the in situ produced (140)Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free (140)Pr(3+). Based upon these results, we conclude that (140)Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free (140)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.