Improved 225Ac daughter retention in InPO4 containing polymersomes.

Alpha-emitting radionuclides like actinium-225 (225Ac) are ideal candidates for the treatment of small metastasised tumours, where the long half-life of 225Ac enables it to also reach less accessible tumours. The main challenge lies in retaining the recoiled alpha-emitting daughter nuclides, which are decoupled from targeting agents upon emission of an alpha particle and can subsequently cause unwanted toxicity to healthy tissue. Polymersomes, vesicles composed of amphiphilic block copolymers, are capable of transporting (radio)pharmaceuticals to tumours, and are ideal candidates for the retention of these daughter nuclides. In this study, the Geant4 Monte Carlo simulation package was used to simulate ideal vesicle designs. Vesicles containing an InPO4 nanoparticle in the core were found to have the highest recoil retention, and were subsequently synthesized in the lab. The recoil retention of two of the daughter nuclides, namely francium-221 (221Fr) and bismuth-213 (213Bi) was determined at different vesicle sizes. Recoil retention was found to have improved significantly, from 37 ± 4% and 22 ± 1% to 57 ± 5% and 40 ± 2% for 221Fr and 213Bi respectively for 100nm polymersomes, as compared to earlier published results by Wang et al. where 225Ac was encapsulated using a hydrophilic chelate (Wang et al. 2014). To better understand the different parameters influencing daughter retention, simulation data was expanded to include vesicle polydispersity and nanoparticle position within the polymersome. The high retention of the recoiling daughters and the 225Ac itself makes this vesicle design very suitable for future in vivo verification.

Retention studies of recoiling daughter nuclides of 225Ac in polymer vesicles.

Alpha radionuclide therapy is steadily gaining importance and a large number of pre-clinical and clinical studies have been carried out. However, due to the recoil effects the daughter recoil atoms, most of which are alpha emitters as well, receive energies that are much higher than the energies of chemical bonds resulting in decoupling of the radionuclide from common targeting agents. Here, we demonstrate that polymer vesicles (i.e. polymersomes) can retain recoiling daughter nuclei based on an experimental study examining the retention of (221)Fr and (213)Bi when encapsulating (225)Ac.

Identification of a homozygous deletion at 8p12-21 in a human prostate cancer xenograft.

One of the most frequent genetic abnormalities in prostate cancer is loss of the complete or part of the short arm of chromosome 8, indicating the localization of one or more tumor suppressor genes on this chromosomal arm. Using allelotyping, a frequently deleted region in prostate cancer in a genetic interval of approximately 17 cM between sequence tagged sites D8S87 and D8S133 at chromosome arm 8p12-21 was previously detected. A detailed physical map of this region is now available. Using known and novel polymorphic and nonpolymorphic sequence tagged sites in this interval, a search for homozygous deletions in DNAs from 14 prostate cancer-derived cell lines and xenografts was carried out. In DNA from xenograft PC133, the presence of a small homozygously deleted region of 730-1,320 kb was unambiguously established. At one site, the deletion disrupts the Werner syndrome gene. Data from allelotyping were confirmed and extended by fluorescence in situ hybridization analysis of PC133 chromosome spreads using centromere, YAC, and PAC chromosome 8 probes.

[Retirement from work; consequences for well-being. A longitudinal analysis]. / Uittreding uit het arbeidsproces; gevolgen voor het welbevinden. Een longitudinale analyse.

Both empirical research and gerontological theories lead to diverging opinions on the effects of finishing the labour process on well-being. On the basis of longitudinal data this paper concludes that the well-being of older persons who retired from the job in the period 1976-1982 did not clearly decrease more than persons who continued working in that period of time. This result still holds in a regression-analysis in which a number of relevant factors are kept constant.