The endogenous amino acid, 5-aminolevulinic acid (5-ALA), has received significant attention as an imaging agent, including ongoing clinical trials for image-guided tumor resection due to its selective uptake and subsequent accumulation of the fluorescent protoporphyrin IX in tumor cells. Based on the widely reported selectivity of 5-ALA, a new positron emission tomography imaging probe was developed by reacting methyl 5-bromolevulinate with [13N] ammonia. The radiotracer, [13N] 5-ALA, was produced in high radiochemical yield (65%) in 10 min and could be purified using only solid phase cartridges. In vivo testing in rats bearing intracranial 9L glioblastoma showed peak tumor uptake occurred within 10 min of radiotracer administration. Immunohistochemical staining and fluorescent imaging was used to confirm the tumor location and accumulation of the tracer seen from the PET images. The quick synthesis and rapid tumor specific uptake of [13N] 5-ALA makes it a potential novel clinical applicable radiotracer for detecting and monitoring tumors noninvasively.
2063 Objectives: The learning objectives are: 1. Introduction of longer distance drone Aircraft Systems (UAS) and its current use in healthcare 2. A review of the fundamental legal and regulatory issues for the use of drones / UAS 3. Needs for efficient longer range distribution of 4. How would a comprehensive approach look like 5. Current developments for a demonstration project in Kenia but designed for general applicability.
Methods: As distribution of imaging pharmaceuticals is highly time critical and Unmanned Aircraft Systems (UAS) are now in place even for delivery of non-essential goods to residential locations and we had previously introduced the concept, we now report on the current state of the art for a country wide delivery concept in Kenia that is being considered for the transport of PET radiopharmaceuticals. Zipline is a drone logistic company specializing in longer range deliveries and has established commercial feasibility and reliability of its operations. New concepts of radiopharmaceutical handling as well as dose management at the receiving side have to be part of such a logistic approach and are enabling to utilize this technology. Synergistically, we had previously demonstrated a low dose / table time optimized approach for whole body FDG PET/CT imaging enabling innovative approaches including advanced reconstruction.
Results: After our previous introduction of the concept of drone transport of imaging pharmaceuticals, we continued to develop a technical design requirement approach in order to facilitate and optimize the process for preparation and handling of the radioactive tracer doses as well as the associated regulatory as well as organizational requirements. While today’s clinical PET/CT operation typically rely on multiple deliveries per day, long distance drone operation will be most efficient by single delivery and efficient use of the delivered pharmaceuticals. This required also the development and validation of count density oriented PET imaging protocols with higher dose and shorter acquisition early after delivery and lower dose longer acquisitions at later time points. While radiopharmaceuticals have been transported in the air for decades, drone transport has different challenges and opportunities. We have identified and conceptualized solutions which will be reviewed.
Conclusions: The need for rapid and efficient transportation even of molecular imaging pharmaceuticals has become more obvious in the re-recent years and even accelerated during the Covid pandemic. In this presentation we introduce the conceptual approaches as well as the current development effort in Kenya to the regional distribution of tracers from a single cyclotron facility as a demonstration project that could be adapted to other environments.
Research Support: This work is supported by the Wright Center of Innovation development fund.
2061 Introduction: Research operations in molecular imaging have always been required to have even more rigorous documentation and organization than even clinical care due to the extensive regulatory and compliance requirements. Operating with minimal staffing in the Covid-19 pandemic era required organizational changes. We performed a system engineering analysis to identify essential process components and developed a process that we referred to as the Amazon- and Google- lization of all process steps. The keys these tech giants use are unique identifiers for everything and every step that enables creation of a unique fingerprint that can then be linked and processed out of any data lake approach using readily available tools like Microsoft Excel or Google sheets. The key process step is to create timestamped events, tasks, or items. The use of QR code labeling, that can be readily scanned by pocket-size QR barcode scanners, is essential and can be accomplished with an inexpensive approach. The linkage of electronic capture forms with the above spreadsheets enables readily implementable optimization with the ability to create and continuous audit trails of every step, item or imaging as well as facility process. In this educational exhibit we will demonstrate how we have implemented this fingerprinting approach and the extensive use of QR labels to have continuous tracking as well as task assignment for process steps from the acquisition of materials to scheduling to capture of radiation safety relevant information and image analysis it. We found that this does not only lead to a tremendous improvement in efficiency of documentation but also helps by being able to assign process step specific tasks that the team member then have in their work you similar to what is in place for clinical radiology information systems. We were surprised that such an operation could be implemented without purchasing any major software utilizing available capabilities of Microsoft 365 and or Google G suite features. Learning objectives A review of using system engineering approaches relevant for research operations The concept of fingerprinting processes and items with unique identifiers and timestamps combined with the continuous audit log to create a comprehensive data repository To introduce how current generation spreadsheet tools can be used for powerful database analysis creating task and process dashboards
1097 Objectives: The objective of the present work was (1) to measure and compare in vitro stability of 68Ga-labeled PSMA targeting conjugates of acyclic and macrocyclic chelators in mouse serum at 37oC, and (2) to correlate stability data with in-vivo tumor uptake in 22Rv1 xenografted mice1. The knowledge of mouse serum stability is critical for the understanding of the efficacy of a potential imaging pharmaceutical.
Methods: Glu-Urea-Lys (GUL) derivatives of acyclic and macrocyclic chelators have been reported as prostate-specific membrane antigen (PSMA) agents. In the present work, GUL was conjugated with two chelators, NOTA and DOTA, via a thiourea linker and designated as NOTA-GUL and DOTA-GUL, respectively. The well-known radioligand PSMA-11, NOTA-GUL, and DOTA-GUL were labeled with 68Ga (37-100 MBq) using a standard radiolabeling technique developed in our laboratories. 68GaCl3 was produced using a Gallia Pharm generator from Eckert & Ziegler. The 68Ga-labeled PSMA conjugates were analyzed and mouse serum stability was monitored by using a reversed-phase High-Performance Liquid Chromatography (RP-HPLC) method. In a typical stability study, a 68Ga-labeled conjugate sample was incubated with mouse serum for 4 hours at 37 °C and the sample was injected onto a RP-HPLC column at a predefined time intervals. Progress of the degradation of the 68Ga-labeled PSMA conjugate in mouse serum was monitored by monitoring area of the main peak with time. Control experiments were performed in each case by monitoring degradation of 68Ga-labeled NOTA-GUL, DOTA-GUL, and PSMA-11 in Phosphate Buffer Saline (PBS).
Results: Efficiency of 68Ga-labeling of NOTA-GUL, DOTA-GUL, and PSMA-11 was achieved >96% with > 99% purity. No degradation of 68Ga-labeled PSMA-11 and NOTA-GUL was observed after 4 h incubation in mouse serum. On the contrary, degradation (mainly demetalation) of 68Ga-labelded DOTA-GUL was seen even after 1 h incubation and reaching up to 8% after 4 h incubation. Consistent with the human serum stability study,1 mouse serum stability of 68Ga-labeled PSMA conjugates followed the order: PSMA-11~NOTA-GUL >DOTA-GUL. A similar trend was observed in the in-vivo tumor uptake (%ID/g) in 22Rv1 xenografted mice 1 h post-injection,i.e 6.5, 5.4, and 4.66 for PSMA-11, NOTA-GUL, and DOTA-GUL, respectively. Interestingly, in the present work 68Ga-labeled DOTA-GUL is less inert than the 68Ga-labeled PSMA-11 in mouse serum.
Conclusions: In summary, the in-vitro mouse serum stability of the three of 68Ga-Labeled PSMA targeting conjugates of acyclic and macrocyclic chelators follow the order PSMA-11~ NOTA-GUL >DOTA-GUL which reflects in the in-vivo tumor uptake in preclinical mice model.1Ref. Moon S-H, Hong MK, Kim YJ et al. Bioorg Med Chem 2018; 26: 2501-2507.
Painful diabetic neuropathy (PDN) is a type of peripheral neuropathic pain that is currently difficult to treat using clinically available analgesics. Recent work suggests a progressive depletion of nitric oxide (NO) in nerve cells may be responsible for the pathobiology of PDN. The nitric oxide donor, 3-methyl-4-furoxancarbaldehyde (PRG150), has been shown to produce dose-dependent analgesia in a rat model of PDN. To gain insight into the mechanism of analgesia, methods to radiolabel PRG150 were developed to assess the in vivo biodistribution in rats. The furoxan ring was labeled with (13)N to follow any nitric oxide release and the 3-methyl substituent was labeled with (11)C to track the metabolite using PET imaging. The in vitro metabolic stability of PRG150 was assessed in rat liver microsomes and compared to in vivo metabolism of the synthesized radiotracers. PET images revealed a higher uptake of (13)N over (11)C radioactivity in the spinal cord. The differences in radioactive uptake could indicate that a NO release in the spinal cord and other components of the somatosensory nervous system may be responsible for the analgesic effects of PRG150 seen in the rat model of PDN.
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