ANSTO Publications Online

Welcome to the ANSTO Institutional Repository known as APO.

The APO database has been migrated to version 7.5. The functionality has changed, but the content remains the same.

ANSTO Publications Online is a digital repository for publications authored by ANSTO staff since 2007. The Repository also contains ANSTO Publications, such as Reports and Promotional Material. ANSTO publications prior to 2007 continue to be added progressively as they are in identified in the library. ANSTO authors can be identified under a single point of entry within the database. The citation is as it appears on the item, even with incorrect spelling, which is marked by (sic) or with additional notes in the description field.

If items are only held in hardcopy in the ANSTO Library collection notes are being added to the item to identify the Dewey Call number: as DDC followed by the number.

APO will be integrated with the Research Information System which is currently being implemented at ANSTO. The flow on effect will be permission to publish, which should allow pre-prints and post prints to be added where content is locked behind a paywall. To determine which version can be added to APO authors should check Sherpa Romeo. ANSTO research is increasingly being published in open access due mainly to the Council of Australian University Librarians read and publish agreements, and some direct publisher agreements with our organisation. In addition, open access items are also facilitated through collaboration and open access agreements with overseas authors such as Plan S.

ANSTO authors are encouraged to use a CC-BY licence when publishing open access. Statistics have been returned to the database and are now visible to users to show item usage and where this usage is coming from.

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[123I]-N-methyl-4iododexetimide: a radioiodinated ligand for SPECT studies of myocardial muscarinic receptors
(Kyoto University, 1983-10-25) Kassiou, M; Katsifis, A; Lamnrecht, RM; Hicks, RJ
Muscarinic cholinergic receptors (mAChR) mediate a closing in the rate of contraction of the heart and a decrease in the force of contraction, while changes in receptor density occur in various physiological, pharmacological and clinic condition. Altered muscarinic receptor distribution in the heart may be a substrate for cardiac arrhythmias and lead to cardiac arrest. Attempts to image myocardial mAChR involves use of radiotracers such as [11C]MQNB and [11C]MTRB with limited SPECT radiotracers avaliable. Recently [1231]-4-iododexetimide (I123]IDEX), a potent mAChR antagonist was used for in vivo studies of myocardial mAChR but proved unsuccessful due to its high lung uptake.‘ We are reporting the preparation and evaluation of the hydrophilic quarternized derivative: [123I]-N-methyl-4-iododexetimide (I123]MIDEX). The radiosynthesis involves firstly preparation of [123I]lDEX by electophilic iododesilylation using trifluoroacetic acid as solvent and chloramine-T as the oxidising agent as described elsewhere} followed by treatment of [123I]IDEX with excess CH3I (fig 1). The methylation reaction is carried out by dissolving [123I]IDEX (10 mCi) in tributyl phosphate (50 µL), a solvent known to promote formation of quaternary ammonium salts, followed by addition of CH3I (300 µL). The reaction mixture was tightly stoppered and heated at 90°C for 15 minutes. After evaporating the excess CH3I and cooling the mixture, isolation and purification of the radiopharmaceutical was carried out by preperative HPLC. A µ-Bondapak C18 column (300 x 7.8 mm) was used while the UV absorption was measured at 239 nm and radioactivity measured on a Berthold system. The mobile phase consisted of acetonitrile and 0.1M ammonium acetate buffer (45:55 v.v) and a flow rate of 2.5 mL/min. The retention times of [123I]IDEX and [123I]MIDEX were 38 and 26 minutes respectively. Radiochemical yields of 80% were reached while radiochemical and chemical purities assessed by HPLC were 97% and the specific activity of [123I]MIDEX was identical to [123]IDEX >2000 mCi/µmol. Rat biodistribution studies were performed and showed high heart uptake (2.4 %ID/g) 10 minutes after injection with a heart to lung radioactivity concentration ratio (H/L) of 5.1. The H/L ratio decreased rapidly to 2.2 after 30 minutes and reached unity at 60 minutes. No uptake of [123I]MIDEX was observed in the brain. The specificity and stereoselectivity of [123I]MIDEX binding at 10 minutes was demonstrated by coinjecting a cold load of levetimide (LEV 0.15 mg/kg), dexetimide (DEX 0.15 mg/kg) and methyl-quinuclidinyl benzylate (MQNB 1 mg/kg) (fig 2). With DEX and MQNB the heart uptake was reduced to 0.20 and 0.13 %1D/g displacing 92% and 95% of the activity respectively while LEV maintained high heart uptake (2.2 %ID/g). Interestingly, the kidney uptake was 21% ID/g and remained constant over a period of 30 minutes. Preliminary SPECT studies carried out on rabbit and dog will also be described. The carbon-11 methylation of dexetimide will also be mentioned. These results suggest that [mI]MIDEX has the potential of being developed as a SPECT radiotracer for the characterisation of myocardial muscarinic receptors.
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Preparation and pharmacological evaluation of a new central muscarinic cholinergic receptor imaging agent [76Br]-4-bromodexetimide
(Kyoto University, 1983-10-25) Kassiou, M; Loc'h, C; Bottlander, MA; Lambrecht, RM; Katsifis, A; Schmid, L; Ottavivani, M; Mazière, M; Mazière , B
Muscarinic cholinergic receptors (mAChR) play an important role in a number of physiological and behavioural responses. The putative role of muscarinic receptors in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease and dementias associated with Parkinson's disease has generated considerable interest for the non invasive mapping of mAChR. Potential muscarinic imaging agents include 11C- and 123I-QNB analogs, 11C-scopolamine and 11C-benztropine while radiolabelled dexetimide derivatives have shown exciting potential. Simpler methods for the preparation of dexetirnide derivatives incorporating. longer lived isotopes suitable forPET studies is required. We are reporting the synthesis and the pharmacological characterisation of a bromine-76 derivative of dexetimide suitable for PET studies. The radiosynthesis of [7‘Br]-4-bromodexetimide ([7‘Br]-BDEX) was carried out by bromination via electrophilic bromodesilylation with no carrier added [76Br]NT-I4. During the preparation of this radiopharmaceutical a number of reaction conditions and reagents were examined. Oxidising agent such as peracetic acid and dichloramine-T were evaluated and found inefficient while chloramine-T appeared the reagent of choice. Peracetic acid reactions were carried out in acetic acid with radiochemical yields of 6% obtained. Dichloromi.ne~T reactions were conducted in both methanol and TFA solvent with radiochemical yields of 10% and 24% respectively. The choramine-T reactions were most efficient but were also concentration and solvent dependent. The optimum labelling conditions were found to be the use of chloramine-T (10-3M) in 0.1N HC1 at room temperature for l5 min followed by addition of a sodium metabisulte solution (fig. 1). Under these conditions the radiochemical yield reaches 80%. The purification and isolation of the radiotracer from the reaction mixture was carried out by HPLC on a µ-Bondapaku-Bondapak C18 column (300 x 7.8 mm) with a mixture of acetonitrile and ammonium acetate buffer (45:55) as the mobile phase and a ow rate of 2.5 ml/min while UV absorption was measured at 239 nm. Radiochemical and chemical purities assessed by radio-TLC and HPLC were 98% with a specific activity of 11 GBq/µmol/L.
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An introduction to the work and facilities of the Australian Atomic Commission Research Establishment
(Australian Atomic Energy Commission, 1958) Australian Atomic Energy Commission
THE AUSTRALIAN ATOMIC ENERGY COMMISSION was created in April, I953, by an Act of Parliament which gave it statutory powers within the constitutional authority of the Commonwealth Government. Its functions concern: - development of practical uses of atomic energy for industrial and other purposes; - scientific research within the commission, and in universities and other institutions; and - training of scientists and engineers to meet the needs of nuclear technology in Australia ; - discovery and production of uranium and nuclear materials. The Head office of the Commission is at 45 Beach Street, Coogee, N.S.W., and is responsible for the general control of all the Commission's activities. ln particular, the Head Office is concerned with policy matters, raw materials (including the Rum Jungle uranium mine and treatment plant), liaison with other Government departments, public and Press relations, extramural and university research' on atomic' energy, and liaison with international and overseas atomic organisations.
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166dysprosium-166holmium in vivo generator
(Kyoto University, 1983-10-10) Mirzadeh, S; Di Bartolo, N; Smith, SV; Lambrecht, RM
Recently, there has been an increasing interest in 166lHo (t1/2=26.8 n, 100% β−, Eβ av=666 Kev) for various therapeutic applications (1-2). A novel approach to deliver this isotope to tissue is via the in-vivo decay of its 81.5-h parent, 166Dy (100% β−, Eβav=l3O MeV) - an in- vivo generator system (3). lt is hoped the flexibility afforded by using this parent-daughter system may result in the reduction of radiation dose to sensitive non-target tissues which until now has limited the efficacy of the radiotherapy. In this scenario, the 166Dy-radiopharmaceutical prepared from pure 166Dy is attached to a tumour specific antibody. During the in vii/0 localisation of the radiolabelled antibody, the resultant dose to non-targeted tissues is reduced because of sub-equilibrium amounts of 166Ho. Once the l66Dy labelled radiopharmaceutical has localised in the target tissue the therapeutic dose can be generated by the decay of its 166Ho daughter. A critical question for the in vivo 166Dy/166Ho generator system is whether translocation of the daughter nucleus occurs following the uptake of the parent at the target site. in an effort to address this question the biodistribution of 166Dg-DTPA was performed, and the bone uptake was carefully analysed for both 166Dy and 166Ho in a gamma-spectrometer employing a Ge(Li) detector. The choice of Dy-DTPA was based on a previous report (4) that the integrity of the 166Ho-DTPA complex is preserved following its formation via 166Dy-DTPA β− decay.
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Carrier-free 166Ho from 166Dy/166Ho biomedical generator system
(Kyoto University, 1983-10-25) Mirzadeh, S; Hetherington, E; Knapp, FF; Lambrecht, RM
Holmium-166 (166 Ho) is a potential candidate for various therapeutic applications (1-2) due to its attractive properties which include emission of high-energy β− particles (Eav=666 MeV), an appropriate half-life (t1/2=26.4 h) and decay to stable daughter. ln addition, 166Ho has chemical characteristics suitable for protein labelling through bifunctional chelates. Holmium-166 also emits a low intensity and low energy γ-rays (80 keV, 6%) suitable for imaging. Due to the absence of high energy γ-rays in its decay, 166Ho may be used for outpatient therapy without significant external radiation to other individuals. Although 166Ho, with a moderate specific activity, can be produced by a simple neutron capture reaction, interestingly, its radionuclidic parent (81 .5-h 166Dy) can serve as a source of high specific activity 166Ho. ln certain applications, such as protein labelling, the use of a high specific activity radioisotope is essential. In addition, generator produced 166Ho is free from 1200-γ 166mHo. This isotope is unavoidably coproduced with 166Ho by the 165Ho[n,γ] reaction (3).