No abstract

By taking advantage of the ability of Cu to bind nonspecifically to gold surfaces, we have developed a methodology to embed this radionuclide inside gold nanoparticles (AuNPs).Cu enables the in vivo imaging of AuNPs by positron emission tomography (PET). AuNPs have a multitude of uses within health technology and are useful tools for general nanoparticle research. Cu-AuNPs were prepared by incubating AuNP seeds withCu, followed by the entrapment of the radionuclide by grafting on a second layer of gold. This resulted in radiolabeling efficiencies of 53 ± 6%. The radiolabel showed excellent stability when incubated with EDTA for 2 days (95% radioactivity retention) and showed no loss of Cu when incubated with 50% mouse serum for 2 days. The methodology was chelator-free, removing traditional concerns over chelator instability and altered AuNP properties due to surface modification. RadiolabeledCu-AuNP cores were prepared in biomedically relevant sizes of 20-30 nm and used to investigate the in vivo stability of three different AuNP coatings by PET imaging in a murine xenograft tumor model. We found the longest plasma half-life (T about 9 h) and tumor accumulation (3.9%ID/g) to result from a polyethylene glycol coating, while faster elimination from the bloodstream was observed with both a Tween 20-stabilized coating and a zwitterionic coating based on a mixture of sulfonic acids and quaternary amines. In the in vivo model, the Cu was observed to closely follow the AuNPs for each coating, again attributed to the excellent stability of the radiolabel.

Background Kidney dosimetry after peptide receptor radionuclide therapy using 177Lu-labelled somatostatin analogues is a procedure with multiple steps. We present the SPECT/CT-based implementation at Aarhus University Hospital and evaluate the uncertainty of the various steps in order to estimate the total uncertainty and to identify the major sources of uncertainty. Absorbed dose data from 115 treatment fractions are reported. Results The total absorbed dose with uncertainty is presented for 59 treatments with [177Lu]Lu-DOTATOC and 56 treatments with [177Lu]Lu-DOTATATE. For [177Lu]Lu-DOTATOC the mean and median specific absorbed dose (dose per injected activity) is 0.37 Gy/GBq and 0.38 Gy/GBq, respectively, while for [177Lu]Lu-DOTATATE the median and mean are 0.47 Gy/GBq and 0.46 Gy/GBq, respectively. The uncertainty of the procedure is estimated to be about 13% for a single treatment fraction, where the absorbed dose calculation is based on three SPECT/CT scans 1, 4 and 7 days post-injection, while it increases to about 19% if only a single SPECT/CT scan is performed 1 day post-injection. Conclusions The specific absorbed dose values obtained with the described procedure are comparable to those from other treatment sites for both [177Lu]Lu-DOTATOC and [177Lu]Lu-DOTATATE, but towards the lower end of the range of reported values. The estimated uncertainty is also comparable to that from other reports and judged acceptable for clinical and research use, thus proving the kidney dosimetry procedure a useful tool. The greatest reduction in uncertainty can be obtained by improved activity determination, partial volume correction and additional SPECT/CT scans.

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.

Mannigfache Zustände: Durch Anbringen zweier Tetrathiafulvalen(TTF)‐Einheiten an einem expandierten Radiaannulen(RA)‐Kern erhält man ein Molekül, das in mehreren Redoxzuständen mit charakteristischen UV/Vis/IR‐Absorptionen existieren kann. Ein niederenergetischer Intervalenzübergang belegt, dass das Radikalkation gemischte Valenzzustände (MV) aufweist.

Ein anelliertes Redoxsystem vom Weitz/Wurster‐Typ wurde durch Verknüpfen eines zentralen erweiterten Radiaannulen‐Kerns mit zwei Tetrathiafulvaleneinheiten erhalten. Das System wird entweder durch Oxidation (6π‐Dithioliumeinheiten) oder durch Reduktion (14π‐Octadehydroannuleneinheit) formal Hückel‐aromatisch und kann in mehreren Redoxzuständen mit charakteristischen UV/Vis/IR‐Absorptionen existieren. Mehr über dieses System kann in der Zuschrift von M. Brøndsted Nielsen et al. auf gefunden werden.

A fused Weitz/Wurster-type redox system … … has been prepared by fusing a central expanded radiaannulene core with two tetrathiafulvalene units. The system formally gains Hückel aromaticity by either oxidation (6p-dithiolium units) or reduction (14p-octadehydroannulene unit) and can exist in several redox states with characteristic UV/Vis/IR absorptions. More about this system can be found in the Communication by M. Brøndsted Nielsen and co-workers on page 6099 ff.