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Simplified programming and control of automated radiosynthesizers through unit operations.

Claggett SB, Quinn KM, Lazari M, Moore MD, van Dam RM - EJNMMI Res (2013)

Bottom Line: The resulting programs were significantly shorter and easier to debug than programs from other systems.We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve.The client-server architecture provided robustness and flexibility.

View Article: PubMed Central - HTML - PubMed

Affiliation: Crump Institute for Molecular Imaging and Department of Molecular and Medical Pharmacology David Geffen School of Medicine, University of California Los Angeles, Building 114, 570 Westwood Plaza, Los Angeles 90095, CA, USA. mvandam@mednet.ucla.edu.

ABSTRACT

Background: Many automated radiosynthesizers for producing positron emission tomography (PET) probes provide a means for the operator to create custom synthesis programs. The programming interfaces are typically designed with the engineer rather than the radiochemist in mind, requiring lengthy programs to be created from sequences of low-level, non-intuitive hardware operations. In some cases, the user is even responsible for adding steps to update the graphical representation of the system. In light of these unnecessarily complex approaches, we have created software to perform radiochemistry on the ELIXYS radiosynthesizer with the goal of being intuitive and easy to use.

Methods: Radiochemists were consulted, and a wide range of radiosyntheses were analyzed to determine a comprehensive set of basic chemistry unit operations. Based around these operations, we created a software control system with a client-server architecture. In an attempt to maximize flexibility, the client software was designed to run on a variety of portable multi-touch devices. The software was used to create programs for the synthesis of several 18F-labeled probes on the ELIXYS radiosynthesizer, with [18F]FDG detailed here. To gauge the user-friendliness of the software, program lengths were compared to those from other systems. A small sample group with no prior radiosynthesizer experience was tasked with creating and running a simple protocol.

Results: The software was successfully used to synthesize several 18F-labeled PET probes, including [18F]FDG, with synthesis times and yields comparable to literature reports. The resulting programs were significantly shorter and easier to debug than programs from other systems. The sample group of naive users created and ran a simple protocol within a couple of hours, revealing a very short learning curve. The client-server architecture provided reliability, enabling continuity of the synthesis run even if the computer running the client software failed. The architecture enabled a single user to control the hardware while others observed the run in progress or created programs for other probes.

Conclusions: We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve. The client-server architecture provided robustness and flexibility.

No MeSH data available.


TLC chromatograms collected post-fluorination and post-purification during an example synthesis of [18F]FDG.
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Figure 7: TLC chromatograms collected post-fluorination and post-purification during an example synthesis of [18F]FDG.

Mentions: After synthesizer initialization, [18F]fluoride produced on an RDS-112 cyclotron (Siemens, Munich, Germany) was trapped on a QMA cartridge and then eluted into reaction vessel 1 (unit operations 1 to 3, Table 3). The [18F]fluoride solution was then dried, and two azeotropic drying steps were performed with acetonitrile (unit operations 4 to 8). A 30-mg mannose triflate precursor dissolved in 1 mL MeCN was then added, and the solution reacted at 130°C for 5 min (unit operations 9 to 10). To demonstrate the ability to take intermediate samples, the ‘INSTALL’ unit operation was placed after the fluorination reaction (after unit operation 10, not listed), and a sample was taken for thin-layer chromatography (TLC) analysis using 95% MeCN in water (v/v) (Figure 7). The solution was subsequently dried at 110°C to remove the MeCN (unit operation 11). After deprotection with HCl (unit operations 12 to 13), the crude product was purified (SCX, ion retardation, Alumina-N, and C18) using the TRANSFER unit operation (unit operation 14) and subsequently rinsed (twice) by adding water to the reaction vessel and transferring it through the purification cartridges (unit operations 15 to 18) and a sterile 0.22-μm filter into a sterile vial. A sample was taken for standard quality assurance testing at our clinical facility.


Simplified programming and control of automated radiosynthesizers through unit operations.

Claggett SB, Quinn KM, Lazari M, Moore MD, van Dam RM - EJNMMI Res (2013)

TLC chromatograms collected post-fluorination and post-purification during an example synthesis of [18F]FDG.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3717018&req=5

Figure 7: TLC chromatograms collected post-fluorination and post-purification during an example synthesis of [18F]FDG.
Mentions: After synthesizer initialization, [18F]fluoride produced on an RDS-112 cyclotron (Siemens, Munich, Germany) was trapped on a QMA cartridge and then eluted into reaction vessel 1 (unit operations 1 to 3, Table 3). The [18F]fluoride solution was then dried, and two azeotropic drying steps were performed with acetonitrile (unit operations 4 to 8). A 30-mg mannose triflate precursor dissolved in 1 mL MeCN was then added, and the solution reacted at 130°C for 5 min (unit operations 9 to 10). To demonstrate the ability to take intermediate samples, the ‘INSTALL’ unit operation was placed after the fluorination reaction (after unit operation 10, not listed), and a sample was taken for thin-layer chromatography (TLC) analysis using 95% MeCN in water (v/v) (Figure 7). The solution was subsequently dried at 110°C to remove the MeCN (unit operation 11). After deprotection with HCl (unit operations 12 to 13), the crude product was purified (SCX, ion retardation, Alumina-N, and C18) using the TRANSFER unit operation (unit operation 14) and subsequently rinsed (twice) by adding water to the reaction vessel and transferring it through the purification cartridges (unit operations 15 to 18) and a sterile 0.22-μm filter into a sterile vial. A sample was taken for standard quality assurance testing at our clinical facility.

Bottom Line: The resulting programs were significantly shorter and easier to debug than programs from other systems.We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve.The client-server architecture provided robustness and flexibility.

View Article: PubMed Central - HTML - PubMed

Affiliation: Crump Institute for Molecular Imaging and Department of Molecular and Medical Pharmacology David Geffen School of Medicine, University of California Los Angeles, Building 114, 570 Westwood Plaza, Los Angeles 90095, CA, USA. mvandam@mednet.ucla.edu.

ABSTRACT

Background: Many automated radiosynthesizers for producing positron emission tomography (PET) probes provide a means for the operator to create custom synthesis programs. The programming interfaces are typically designed with the engineer rather than the radiochemist in mind, requiring lengthy programs to be created from sequences of low-level, non-intuitive hardware operations. In some cases, the user is even responsible for adding steps to update the graphical representation of the system. In light of these unnecessarily complex approaches, we have created software to perform radiochemistry on the ELIXYS radiosynthesizer with the goal of being intuitive and easy to use.

Methods: Radiochemists were consulted, and a wide range of radiosyntheses were analyzed to determine a comprehensive set of basic chemistry unit operations. Based around these operations, we created a software control system with a client-server architecture. In an attempt to maximize flexibility, the client software was designed to run on a variety of portable multi-touch devices. The software was used to create programs for the synthesis of several 18F-labeled probes on the ELIXYS radiosynthesizer, with [18F]FDG detailed here. To gauge the user-friendliness of the software, program lengths were compared to those from other systems. A small sample group with no prior radiosynthesizer experience was tasked with creating and running a simple protocol.

Results: The software was successfully used to synthesize several 18F-labeled PET probes, including [18F]FDG, with synthesis times and yields comparable to literature reports. The resulting programs were significantly shorter and easier to debug than programs from other systems. The sample group of naive users created and ran a simple protocol within a couple of hours, revealing a very short learning curve. The client-server architecture provided reliability, enabling continuity of the synthesis run even if the computer running the client software failed. The architecture enabled a single user to control the hardware while others observed the run in progress or created programs for other probes.

Conclusions: We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve. The client-server architecture provided robustness and flexibility.

No MeSH data available.