Neodymium-140 DOTA-LM3: Evaluation of anGenerator for PET with a Non-Internalizing Vector

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Gregory W Severin, Lotte K Kristensen, Carsten H Nielsen, Jesper Fonslet, Andreas I Jensen, Anders F Frellsen, K M Jensen, Dennis R Elema, Helmut Maecke, Andreas Kjær, Karl Johnston, Ulli Köster

140 Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter140Pr (t1/2 = 3.4 min), has promise as anin vivogenerator for positron emission tomography (PET). However, the electron capture decay of140Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that anin vivoredistribution of the daughter140Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled140Pr affects preclinical imaging with140Nd. To explore the effect,140Nd 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 thein vivoredistribution of140Pr following140Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of140Nd-DOTA-LM3 (13% ID/g at 16 h) coupled with the largest observed redistribution rate, where 56 ± 7% (n = 4, mean ± SD) of thein situproduced140Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free140Pr3+. Based upon these results, we conclude that140Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free140Pr. This redistribution phenomenon may show promise as a probe of the cellular interaction with the vector, such as in determining tissue dependent internalization behavior.

Original languageEnglish
Article number98
JournalFrontiers in Medicine
Number of pages9
Publication statusPublished - 2017

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