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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.

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