Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226.     

Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: possible role in thyroid-associated ophthalmopathy

OBJECTIVE Smoking is a risk factor for the development of thyroid-associated ophthalmopathy, an inflammatory process primarily affecting the fibroblasts in extraocular muscles. We wished to determine whether the extraocular muscle fibroblasts are more sensitive than dermal fibroblasts to T-cell derived cytokines, as a reason for this anatomical localization, and whether hypoxia alters fibroblast function, as one explanation for the susceptibility conferred by smoking. DESIGN Fibroblasts derived from the skin or extraocular muscles of healthy subjects were cultured with cytokines under normal (5% CO₂:95% air) and hypoxic (5% C0₂:95% N₂) conditions. MEASUREMENTS Glycosaminoglycan, protein and DNA synthesis were measured by assessing incorporation of d -6-³H-glucosamine, ³H-amino acids, and ³H-thymidine respectively. RESULTS α-lnterferon and interleukin-6 had no effect on fibroblasts, γ-Interferon, tumour necrosis factor and inter-leukin-1 stimulated glycosaminoglycan synthesis; this effect was greater in orbital than in dermal fibroblasts with γ-interferon and interleukin-1 (P<0.05). The same cytokines stimulated total protein with a greater response in orbital fibroblasts with γ-interferon. Interleukin-1 inhibited DNA synthesis in orbital fibroblasts but stimulated DNA synthesis in dermal fibroblasts (P< 0.01); tumour necrosis factor also displayed a differential effect (P<0.01). Hypoxia caused a significant increase in glycosaminoglycan, protein and DNA synthesis in both types of fibroblasts, under both basal and cytokine-treated conditions (P < 0.05). CONCLUSIONS Extraocular muscle fibroblasts respond differently from dermal fibroblasts following cytokine stimulation, which may explain in part the anatomical localization of ophthalmopathy. Hypoxia stimulates fibroblasts and this could contribute, as an enhancing factor, to the adverse effects of smoking on thyroid eye disease.     

Mapping the Distribution of the Telomeric Sequence (T2AG3) n in the 2n = 14 Ancestral Marsupial Complement and in the Macropodines (Marsupialia: Macropodidae) by fluorescence in situ hybridization

In this study we test the theory that the presence of the conserved vertebrate telomeric sequence (T(2)AG(3))(n) at the centromeres of Australian marsupial 2n = 14 complements is evidence that these karyotypes are recently derived, which is contrary to the generally held view that the 2n = 14 karyotype is ancestral for Australasian and American marsupials. Here we compare the distribution of the (T(2)AG(3))( n ) sequence and constitutive heterochromatin in the presumed ancestral 2n = 14 complement and in complements with known rearrangements. We found that where there were moderate to large amounts of constitutive heterochromatin, the distribution of the (T(2)AG(3))(n) sequence reflected its presence as a native component of satellite DNA rather than its involvement in past rearrangements. The presence of centromeric heterochromatin in all Australian 2n = 14 complements therefore suggests that centromeric sites of the (T(2)AG(3))(n) sequence do not represent evidence for recent rearrangements.     

Modelling polychromatic high energy photon beams by superposition

A unified three dimensional superposition approach to dose calculations used in treatment planning of polychromatic high energy photon beams in radiotherapy is developed. The approach we have used involves computing the dose at all points in a medium by superposing the dose spread array (DSA) from the interaction of a photon at a point in the medium with an array of data representing the TERMA (photon fluence times the photon energy) at points in the beam. The polychromatic nature of the beam is accounted for by modelling the beam as having ten spectral components. A "polychromatic dose spread array" (PDSA) for an interaction from a beam with this spectrum was derived. The TERMA array is calculated from a weighted average of the TERMA arrays for the ten photon energies to give a "polychromatic TERMA array". Thus the method accounts for the effect of beam hardening of the TERMA. But it does not account for the effect of beam hardening on the PDSA since a single PDSA (usually for the spectrum at the surface of the medium) is used at all depths. However, by considering measured and calculated beam central axis data, this model is shown to be adequate for computing depth doses for beams in a homogeneous medium penetrating to extreme radiological depths. A computation time advantage is gained because only one superposition per beam is required.