Automated processing of solid target 86Y using enriched SrO powder.

86Y (t1/2 = 14.74 h, 32% ß+) has significant potential in theranostic applications as a simultaneous PET imaging partner to 90Y-labelled antibody therapy. However, the complex and costly nature of producing 86Y has led to this radiometal being difficult for hospitals and researchers to obtain. The aim of this work was to develop a simple and cost-efficient method for safely producing 86Y. Our approach was twofold: to develop a method of target preparation that would significantly increase the cost efficiency of producing 86Y, and to design and construct an automated purification system that would eliminate manual radiation handling risks and exposure. Multiple automated productions of high radionuclidic purity (99.45%) 86Y were performed resulting in saturation yields of between 518 MBq/µA and 1332 MBq/µA, dependent on target thickness.

Quality of radiochemical purity in multiple samples of various fractionated cold kits: Testing a cost & time effective technique.

OBJECTIVE: This study was aimed to assess technical aspects of fractionation of commonly used cold kits in Nuclear Medicine. MATERIALS AND METHODS: A total of 90 samples (30 samples each) of technetium-99m methylene diphosphonate (99mTc-MDP), 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 99mTc-dimercaptosuccinic acid (DMSA III) were taken on various days. The radiochemical purity was calculated of each fraction of these cold kits by using paper chromatography. RESULTS: The mean value of radiochemical purity of 99mTc -MDP, 99mTc -DTPA and 99mTc-DMSA(III) were calculated as ~ 95.12%, 91.43% and 95.68% and standard deviation (SD) were ~ 5.43, 8.36 and 3.88, respectively. Maximum time in which fractionation procedure completed i.e. time required for preparing the fraction or thawing was 10 minutes. All fractionated aliquots were between 1 and 15 days. Radiopharmaceutical bio-distribution was found to be appropriate during imaging in all samples. CONCLUSION: Fractionation of cold kits using standardised technique is a time and cost-effective method and does not deteriorate the quality of labelling in commonly used pharmaceuticals in our study. We have used fractionated aliquots up to 3 days of preparation in patients with clinically usable radiochemical purity. Deep frozen fractions can be used up to 15 days in our experience.

"In-loop" 18 F-fluorination: A proof-of-concept study.

There is a great demand to develop more cost-efficient and robust manufacturing processes for fluorine-18 (18 F) labelled compounds and radiopharmaceuticals. Herein, we present to our knowledge the first radiofluorination "in-loop," where [18 F]triflyl fluoride was used as the labelling agent. Initial development of the "in-loop" [18 F]fluorination method was optimized by reacting [18 F]triflyl fluoride with 1,4-dinitrobenzene to form [18 F]1-fluoro-4-nitrobenzene. This methodology was then applied for the syntheses of two well-known radiopharmaceuticals, namely, [18 F]T807 for imaging of tau protein and [18 F]FEPPA for imaging the translocator protein 18 KDa. Both radiotracers were synthesized and formulated using an automated radiosynthesis module with nondecay corrected radiochemical yields of 27% and 29% (relative [18 F]F- ), respectively. The overall syntheses times for [18 F]T807 and [18 F]FEPPA were 65 and 55 minutes, respectively. In these cases, our "in-loop" radiofluorination methodology enabled us to obtain equal or superior yields compared with conventional reactions in a vial. The radiochemical purities were more than 99%, and the molar activities were more than 350 GBq/µmol at the end-of-synthesis for both radiotracers. This novel method is simple, efficient, and allows for a reliable production of radiofluorinated compounds and radiopharmaceuticals.

Fast and cost-effective cyclotron production of 61Cu using a natZn liquid target: an opportunity for radiopharmaceutical production and R&D.

Following our previous work on the production of radiometals, such as 64Cu and 68Ga, through the irradiation of liquid targets using a medical cyclotron, we describe in this paper a technique to produce 61Cu through the irradiation of natural zinc using a liquid target. The proposed method is very cost-effective, as it avoids the use of expensive enriched material, and is fast, as a purified solution of 61CuCl2 is obtained in less than 30 min after the end of beam. Considering its moderate half-life of 3.33 h and favourable decay properties as a positron emitter, 61Cu is a very attractive nuclide for the labelling of PET tracers for pre-clinical and clinical use with PET as well as to support the intense R&D programmes being carried out worldwide by taking advantage of the rich and versatile chemistry of copper.

Diversification of 99Mo/99mTc separation: non­fission reactor production of 99Mo as a strategy for enhancing 99mTc availability.

This paper discusses the benefits of obtaining (99m)Tc from non-fission reactor-produced low-specific-activity (99)Mo. This scenario is based on establishing a diversified chain of facilities for the distribution of (99m)Tc separated from reactor-produced (99)Mo by (n,γ) activation of natural or enriched Mo. Such facilities have expected lower investments than required for the proposed chain of cyclotrons for the production of (99m)Tc. Facilities can receive and process reactor-irradiated Mo targets then used for extraction of (99m)Tc over a period of 2 wk, with 3 extractions on the same day. Estimates suggest that a center receiving 1.85 TBq (50 Ci) of (99)Mo once every 4 d can provide 1.48-3.33 TBq (40-90 Ci) of (99m)Tc daily. This model can use research reactors operating in the United States to supply current (99)Mo needs by applying natural (nat)Mo targets. (99)Mo production capacity can be enhanced by using (98)Mo-enriched targets. The proposed model reduces the loss of (99)Mo by decay and avoids proliferation as well as waste management issues associated with fission-produced (99)Mo.

Diversification in the Supply Chain of (99)Mo Ensures a Future for (99m)Tc.

The uncertain availability of (99m)Tc has become a concern for nuclear medicine departments across the globe. An issue for the United States is that currently it is dependent on a supply of (99m)Tc (from (99)Mo) that is derived solely by production outside the United States. Since the United States uses half the world's (99)Mo production, the U.S. (99)Mo supply chain would be greatly enhanced if a producer were located within the United States. The fragility of the old (99)Mo supply chain is being addressed as new facilities are constructed and new processes are developed to produce (99)Mo without highly enriched uranium. The conversion to low-enriched uranium is necessary to minimize the potential misuse of highly enriched uranium in the world for nonpeaceful means. New production facilities, new methods for the production of (99)Mo, and a new generator elution system for the supply of (99m)Tc are currently being pursued. The progress made in all these areas will be discussed, as they all highlight the need to embrace diversity to ensure that we have a robust and reliable supply of (99m)Tc in the future.

A sensitive, rapid and inexpensive method to assess aluminium(III) ions in technetium eluates.

The aim of the study was to validate a semiquantitative analytical method to identify the aluminium(III) [Al(III)] concentration in 99Mo/99mTc generator eluates to check the European Pharmacopoeia (Ph. Eur.) requirement (<5 µg/ml). Three different solutions measuring 20 ml - 0.2% 1,10-phenanthroline, 0.05% chrome azurol S and 20% hexamethylenetetramine - were prepared. A cellulose filter paper was subsequently immersed in them, dried overnight at room temperature and cut into rectangles. A volume of 5 µl of first eluates of various 99Mo/99mTc generators was placed onto a reagent paper and the spot colour was compared with a standard aluminium solutions scale (0-100 µg/ml). A cyan/magenta/yellow/key (CMYK) model analysis was adapted to quantify the intensity of colour on the paper, and the presence of aluminium in the eluates was detected by a spectrophotometer. Small changes in standard solution pH (4.1-5.2) and chrome azurol S concentration did not affect the analysis. The cyan channel image analysis was proportional to the Al3+ solution concentration (y=25 019x+1489, R2=0.9554 within 2.5-8 µg/ml). The detection limit for aluminium by the visual test method is about 1 µg/ml, and fading is absent. The cyan channel image analysis method is independent of the observer and is applicable for the evaluation of the chemical purity of 99Mo/99mTc generator eluates. Our colorimetric 'spot test' is advantageous for the visual evaluation of Al pertechnetate concentrations as required by Ph. Eur. showing a sensitivity and a limit of detection superior to that of commercially available spot systems.

18FDG synthesis and supply: a journey from existing centralized to future decentralized models.

Positron emission tomography (PET) as the functional component of current hybrid imaging (like PET/ CT or PET/MRI) seems to dominate the horizon of medical imaging in coming decades. 18Flourodeoxyglucose (18FDG) is the most commonly used probe in oncology and also in cardiology and neurology around the globe. However, the major capital cost and exorbitant running expenditure of low to medium energy cyclotrons (about 20 MeV) and radiochemistry units are the seminal reasons of low number of cyclotrons but mushroom growth pattern of PET scanners. This fact and longer half-life of 18F (110 minutes) have paved the path of a centralized model in which 18FDG is produced by commercial PET radiopharmacies and the finished product (multi-dose vial with tungsten shielding) is dispensed to customers having only PET scanners. This indeed reduced the cost but has limitations of dependence upon timely arrival of daily shipments as delay caused by any reason results in cancellation or rescheduling of the PET procedures. In recent years, industry and academia have taken a step forward by producing low energy, table top cyclotrons with compact and automated radiochemistry units (Lab- on-Chip). This decentralized strategy enables the users to produce on-demand doses of PET probe themselves at reasonably low cost using an automated and user-friendly technology. This technological development would indeed provide a real impetus to the availability of complete set up of PET based molecular imaging at an affordable cost to the developing countries.

A radiochemical technique with potential for revealing novel fungal metabolites according to expression of specific biosynthetic activities.

Fungal secondary metabolites are mostly derived from a few key intermediates in primary metabolism, such as acetate and some amino acids. Classical screens for novel fungal compounds of possible industrial interest have used chromatographic displays of extract components, as was the practice for plant natural products, followed by structural determination and pharmacological study. In contrast, modern robotic screens usually focus initially on specific bioassay applied to fermentation products and crude extracts. Both strategies are expensive in terms of human resources and/or in sophisticated equipment. A relatively inexpensive technique, exploiting biosynthetic principles through use of 14C-labelled probes to recognise particular structural features by autoradiography of tlc plates is described and discussed. Application to 80 isolates of filamentous fungi from Caribbean and European/Mediterranean environments enabled recognition of arrays of metabolites according to their biosynthetic origin, showing the potential of the technique in novel product discovery in unsophisticated laboratory facilities, as exemplified by reference to subsequent discovery of novel metabolites produced by Amorosia littoralis.