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

Abstract

140Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter 140Pr (t1/2 = 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.

A solid support generator of the Auger electron emitter rhodium-103m from [103Pd]palladium

“…The phenomenon is especially interesting in the radiopharmaceutical use of radiometal chelates with radioactive daughters. Here, the decay of the parent may expel the daughter from the chelator, resulting in a free radioactive species with its own pharmacokinetics (Edem et al, 2016;Severin et al, 2017;Kozempel, 2018). The effect has also been utilized for the preparation of radionuclide generators.…”

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“…NCI-H727 [59] is the most used cell line for the study of typical carcinoma. This cell line has been used to test several compounds or molecular imaging techniques in different studies [60][61][62][63][64][65]. However, the characteristics of the primary tumors originating from this cell line are not consistent with the biology of a typical carcinoid, thus hampering the understanding of the molecular mechanisms underlying this tumor type.…”

The Use of the Macrocyclic Chelator DOTA in Radiochemical Separations

“…In order to avoid the release of 140 Pr to design an in vivo generator for this pair should try to use open‐chain chelators such as e.g. DTPA derivatives instead of DOTA …”