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

¹⁴⁰Nd (t_1/2 = 3.4 days), owing to its short-lived positron emitting daughter ¹⁴⁰Pr (t_1/2 = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of ¹⁴⁰Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter ¹⁴⁰Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled ¹⁴⁰Pr affects preclinical imaging with ¹⁴⁰Nd. 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 the in vivo redistribution of ¹⁴⁰Pr following ¹⁴⁰Nd decay. The somatostatin receptor-positive pancreas exhibited the highest tissue accumulation of 140Nd-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 ¹⁴⁰Pr washed out of the pancreas before decay. Contrastingly, the liver, spleen, and lungs acted as strong sink organs for free ¹⁴⁰Pr³⁺. Based upon these results, we conclude that ¹⁴⁰Nd imaging with a non-internalizing vector convolutes the biodistribution of the tracer with the accumulation pattern of free ¹⁴⁰Pr. This redistribution phenomenon may show promise as a probe of the cellular interaction with the vector, such as in determining tissue dependent internalization behavior.