[en] The chemical similarity of technetium and rhenium has created much interest in the nuclear medicine field to make a 'matched pair' of radiopharmaceuticals for radioimmuno- diagnosis and therapy. Clinical trials with the ⁹⁹mTc-DD-3B6/22 Fab' has shown promise in the diagnosis of ovarian cancer. The design of the analogous therapeutic agent with rhenium-188 (155 keV γ 15 % abundant, β E_max 2.1 MeV, T 1/2 17 h) is under investigation. The present study describes the approach taken for direct radiolabelling of the DD-3B6/22 Fab' with carrier-free ¹⁸⁸Re and its biological evaluation in balb/c and nude mice. The effect of temperature, pH and antibody concentration on the amount and rate of transchelation was also evaluated. The final product had a specific activity of 35 mCi/mg with an immunoreactive fraction of 77%. Stability of the product was assessed under various conditions: temperature, presence and absence of an inert atmosphere and presence of ascorbic acid (stabilised). Pharmacokinetics of the final product was evaluated in balb/c and nude mice transplanted with both D-dimer (+Ve) and Glycine (-Ve) beads. Results show that ¹⁸⁸Re DD-3B6/22 Fab' clears rapidly from the blood (α = 2.4 hr, β = 3.5 hr) and is excreted through the renal system. Localisation to subcutaneous antigen beads shows specific uptake to the D-dimer (antigen) beads was achieved within 6 h (0.23% ID) and was maintained for 24 hour post injection. Specificity to antigen implants was 5:1 (P <0.001) when compared to non-specific bead implants. These results correlate well with those obtained for the ^99m Tc DD-3B6/22 Fab' in mice. The radiolabelling procedures are congenial for therapeutic levels and hence the authors believe that the ¹⁸⁸Re DD-3B6/22 Fab' has some potential for use in treatment of ovarian cancer

[en] New approaches to killing chemoresistant and radioresistant hypoxic cells of solid tumours include the selective release of potent cytotoxins from relatively non-toxic prodrugs through reductive metabolism and/or radiolytic reduction. Central to these studies, is an understanding of the mechanism of cytotoxin release and the basis of hypoxia-selectivity, since such information can be used to design compounds of high potency against solid tumours. Pulse radiolysis studies can offer unique insights into these underlying mechanisms in aqueous solution through the determination of thermodynamic one-electron reduction potentials of the prodrugs, rate constants for the formation and spectral charaterization of one-electron reduced prodrugs, the kinetics release of the cytotoxins from one-electron reduced prodrugs and the influence of molecular oxygen on the obligate radical intermediates. A series of different triggers, which are found to vary greatly in the rate constant for release of the effectors upon one-electron reduction of the prodrugs, will be discussed. Release of effector from a prodrug does not solely depend upon the type of trigger but can also be dependent on the type of linker and released effector. For example, whereas fast quantitative release of the mustard effector mechlorethamine is seen from the quaternary nitroimidazole upon one electron reduction, release of N-[2-(dimethylamino)ethyl] acridine-4-carboxamide (DACA), requires a higher level of reduction of the same trigger. Release of cytotoxic ligands from metal complexes requires that the metal centre is reduced. When the metal centre is lower than DACA bound as a ligand, reduction is seen to occur solely on the ligand without release from the metal centre

[en] Crypt survival in the mouse intestine has been used to examine effects of bisbenzimide radioprotectors. Intravenous delivery has been used for the present study in which the effects of methyl proamine (MP), a second generation Hoechst 33342 analogue have been examined. Recent results using the lung model suggest that MP is both more potent as a protector and less toxic than H 33342. The rapid nature of the crypt microcolony survival assay in mouse intestine provides an efficient way to examining factors which could impinge on the extent of radioprotection, for example, the interval between protector administration and radiation exposure. The data clearly show that for MP at 100 mg/kg, there is substantially increased crypt survival equivalent to a dose modification of about 1.33. The crypt scoring methods used indicate that protection is throughout the small intestine and preliminary data indicate that colon is also protected to a similar or slightly greater extent

[en] By measuring the linear energy transfer (LET) spectrum with a microdosimeter a valuable information for calculation of the biological efficiency of a medical radiation beam can be obtained. An optimal microdosimeter should have the sensitive volume of a cellular size and even represent a biological cell on a subcellar level for understanding deposited energy pattern in nuclear and cytoplasmic cell structures. An approach to microdosimetry, which satisfies the above criteria, models a biological cell with a silicon micro size cell. The quantitative measurement of deposited energy pattern by charge spectroscopy in a p-n junction with the size of a typical biological cell is a further step in characterisation of a mixed radiation environment. Such a dosimeter incorporates integral MOSFET dosimetry and charge collection spectroscopy in practically the same geometric volume. The integral dose has been measured using threshold voltage shift and the spectrum of deposited charge has been measured using the drain n⁺-p junction as a dE/dx detector. These measurements were performed simultaneously on the same MOSFET detector chip. Integral response of a MOSFET dosimeter was measured for ²¹⁰Po and ²⁴¹Am alpha particles at a range of bias voltages. It was shown that contribution of a ²⁴¹Am 59.9 keV x-ray to the MOSFET threshold voltage change was insignificant and decreases with the bias voltage. The pulse height spectra were measured for ²¹⁰Po and ²⁴¹Am alpha particles, photons emitted by a ⁶⁰Co source and beta particles from a ⁹⁰Sr. For alpha particles spectra were measured for two different connection modes at different bias voltages. The changes in the spectra are discussed. Practical application of the MOSFET microdosimeters for separation of high and low LET radiation were done at radiation oncology facility at Brookhaven Medical Research Reactor. Some results of this study are to be discussed

[en] Full text: A double-stranded oligodeoxynucleotide containing ¹²⁵I-dC in a defined location, with 5'- or 3'-³²P-end-labelling of either strand, was used to investigate DNA strand breakage resulting from ¹²⁵I decay. Samples of the ³²P-end-labelled and ¹²⁵I-dC containing oligoDNA were incubated in 20 mM phosphate buffer (PB), or PB + 2 M dimethylsulphoxide (DMSO) at 4 deg during 18-20 days. The ³²P-end-labelled DNA fragments produced by ¹²⁵I decays were separated on denaturing polyacrylamide gels, and the ^3P activity in each fragment was determined by scintillation counting after elution from the gel. The fragment size distribution was then converted to a distribution of single stranded break probabilities at each nucleotide position. The results indicate that each ¹²⁵I decay event produces at least one break in the ¹²⁵I-dC containing strand, and causes breakage of the opposite strand in 75-80% of events. Thus, the double stranded break is produced by ¹²⁵I decay with probability ∼0.8. Most of single stranded breaks (around 90%) occurred within 5-6 nucleotides of the ¹²⁵I-dC, however DNA breaks were detected up to 18-20 nucleotides from the decay site. The average numbers of single stranded breaks per decay are 3.7 (PB) and 3.3 (PB+DMSO) in ¹²⁵I-dC containing strand, and 1.5 (PB) and 1.3 (PB+DMSO) in the opposite strand. Deconvolution of strand break probabilities as a function of separation from the ¹²⁵I, in terms of both distance (to target deoxyribosyl carbon atoms, in B-DNA) and nucleotide number, show that the latter is an important parameter for the shorter-range damage. This could indicate a role for attenuation/dissipation of damage through the stacked bases. In summary, the results represent a much more extensive set of data than available from earlier experiments on DNA breakage from ^l25I-decay, and may provide new mechanistic insights

[en] Full text: Copolymers of butadiene (BD) and acrylonitrile (AN) (NBR rubber), have become important commercial material. NBR rubbers are part of a larger classification of products often referred to as special-purpose rubbers. Oil resistance is the most important property of nitrile rubbers, and refer to the ability of the vulcanised product to retain its original physical properties such as modulus, tensile strength, abrasion resistance and dimensions, while in contact with oils and fuels. Despite these reported advantages very few studies have been conducted on the radiation yields and structural changes in nitrile rubbers during exposure to high energy radiation. In this study we are investigating the stability against gamma and UV radiation, to different doses in vacuum, of butadiene, acrylonitrile and NBR copolymers with different composition ratio BD/AN. The mechanism of radiation induced structural changes is being investigated using experimental techniques such as ESR, NMR (Solid-state), FT-IR, RAMAN and UV spectroscopy. Also is being investigated the effect of irradiation on the mechanical properties of stressed and unstressed samples by TGA, DSC, DMA, Instron and Creep Test measurements. So far the main effect have been a marked radiation-induced loss of unsaturation in the butadiene units, cis to trans isomerization and formation of crosslink structures (intermolecular and intramolecular). One of the main challenges in the studies of NBR polymers is to observe directly the crosslinks produces by the radiation induced chemical reactions. IR spectroscopy is unsuitable because of the low molar absorbity of the peaks related to intermolecular crosslinking and the overlapping of the peaks (1630-1670 cm-1) related to intramolecular crosslinking (cyclization), with conjugated and nonconjugated (-C=C-; -C=N-) double bonds. A. K. Whittaker has shown that crosslink structures in PBD can be detected and measured directly using solid-state ¹³C NMR. This technique, and others, will allow us to detect and quantify the radiation induced chemical effects in nitrile rubber

[en] Intense flux of fast neutrons are produced during routine isotope production runs at the National Medical Cyclotron. These stray neutrons induce irreversible displacement damage in the semiconductor devices, the vital building blocks of the various electronic instruments used in the facility. This poster highlights the results of the radiation hardness investigation study of commercial silicon diodes undertaken at the Health Physics laboratory of the National Medical Cyclotron

[en] In this study, thermotropic liquid crystalline poly (allylsulfone)s which have different end groups on the side chain such as cyano, nitro, methoxy, phenyl, and chloro have been synthesised. The effect of γ-radiation have been investigated using CP-MAS-NMR, DSC, X-ray diffractometry and CP-microscopy

[en] The difference in incidence of radiation-induced apoptosis between two neonatal urogenital tissues, kidney and testis, was analysed over a 24h period. Concurrent administration of cycloheximide (10mg/kg body weight), a protein synthesis inhibitor, with radiation treatment was used to determine whether new protein synthesis had a role in induction of apoptosis in this in vivo model. Many chemotherapeutic drugs act via protein synthesis inhibition, and we believe that the results of this latter analysis may provide information for the planning of concurrent radio and chemotherapy. Apoptosis was quantified using morphological parameters, and verified by DNA gel electrophoresis for the typical banding pattern, and by electron microscopy. The proliferative index in tissues was studied, using [6-³H]-thymidine uptake ( 1h prior to euthanasia and collection of tissues) and autoradiography as indicators of cell proliferation (S-phase). Tissue was collected 2, 4, 6, 8, and 24h after radiation treatment. Expression of one of the apoptosis-associated genes, Bcl-2 (an apoptosis inhibitor/cell survival gene), was studied using immunohistochemistry. Apoptosis peaked at 4h in the testis and 6h in the kidney, emphasising the necessity of knowing tissue differences in radiation response if comparing changes at a particular time. A higher proportion (almost five fold) of the apoptotic cells died in S-phase in the kidney than the testis, over the 24h. Protein synthesis inhibition completely negated induction of apoptosis in both tissues. Necrosis was not identified at any time. Cycloheximide treatment greatly diminished Bcl-2 expression. The differences in response of the two tissues to irradiation relates to their innate cell (genetic) controls, which may be determined by their state of differentiation at time of treatment, or the tissue type. This in vivo study also suggests the model may be useful for analysis of other cancer therapies for example polychemotherapies or chemo-and radiotherapy

[en] Full text: The curing of two phenylethynyl terminated composite resins was investigated under thermal and γ-irradiation conditions. The resins, PETI5A and DFB/BPF have been specially developed by NASA for high temperature aerospace applications, and as such have been synthesised with a high degree of aromaticity and hence lack of aliphatic protons. The thermal curing occurs via the thermal decomposition of the resin to form radicals which initiate the addition polymerisation which proceeds through the ethynyl units. The decomposition processes at the cure temperature of 360 deg C lead to the formation of a very dark coloured resin. The radiation cured resin was significantly lighter in colour, indicating less degradation of the resin. In order to reduce the degree of thermal decomposition during polymerisation, γ- radiation induced cure was attempted at 300 deg C. The loss of ethynyl bonds was monitored for both the thermal and radiation induced curing with FT-Raman Spectroscopy and the formation of a polymer network was observed using Differential Scanning Calorimetry (DSC). The maximum Glass Transition Temperatures (Tg) for the resins was found to be 245 ± 2 deg C for DFB/BPF in 60 minutes and 360 ± 2 deg C for PETI5A in 100 minutes for thermal cure at 360 deg C. Similar values were observed after γ-irradiation to doses of approximately 40 kGy for DFB/BPF and 80 kGy for PETI5A when irradiated at 300 deg C. Thermogravimetric Analysis (TGA) shows us that the thermal decomposition process is 100 times less apparent at 300 deg C than at 360 deg C