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

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

JOURNAL=Frontiers in Medicine

VOLUME=4

YEAR=2017

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2017.00098

DOI=10.3389/fmed.2017.00098

ISSN=2296-858X

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