Barnhart, Todd E.

Cai, Weibo

Ellison, Paul A.

Engle, Jonathan W.

Fonslet, Jesper

Graves, Stephen A.

Nickles, Robert J.

Severin, Gregory

Valdovinos, Hector F.

Online Research Database In Technology

General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from orbit.dtu.dk on: Dec 21, 2017Optimized 52Mn Production for Longlived PET ApplicationsGraves, Stephen A.; Severin, Gregory; Valdovinos, Hector F.; Fonslet, Jesper; Ellison, Paul A.; Barnhart,Todd E.; Engle, Jonathan W.; Cai, Weibo; Nickles, Robert J.Published in:Proceedings - World Molecular Imaging Congress 2015Publication date:2015Document VersionPeer reviewed versionLink back to DTU OrbitCitation (APA):Graves, S. A., Severin, G., Valdovinos, H. F., Fonslet, J., Ellison, P. A., Barnhart, T. E., ... Nickles, R. J. (2015).Optimized 52Mn Production for Longlived PET Applications. In Proceedings - World Molecular ImagingCongress 2015CONTROL ID: 2230875TITLE: Optimized 52Mn Production for Long­lived PET ApplicationsAUTHORS (FIRST NAME, LAST NAME): Stephen Graves1, Gregory W. Severin2, HectorF. Valdovinos1, Jesper Fonslet2, Paul Ellison1, Todd E. Barnhart1, Jonathan W. Engle3,Weibo Cai1, Robert J. Nickles1ABSTRACT BODY: Abstract Body: Introduction52Mn (t​1/2 =5.59 d, ß+ = 29.6%, Eßmax = 0.58 MeV) presents itself as an excellent candidatefor a variety of PET applications. Chelation of 52Mn would allow for radiolabelled antibodyimaging 2­4 weeks post­injection, and free 52Mn2+ has shown promise as a reporter geneprobe in stem cell tracking applications [1]. The goals of this work were to develop an efficient52Mn production target, to optimize separation chemistry, and to demonstrate effectivechelation.Methods52Mn was produced by 16 MeV proton irradiation of natural chromium metal (approximately750 mg, 99.999%, GFS chemicals) hydraulically pressed into 0.5 mm thick silver disk. Withdirect jet water cooling on the rear face, these targets were shown to withstand 60 µA of beamcurrent for one hour without failure. Targets were etched by 2 mL 12.1M HCl and then dilutedwith 48 mL ethanol and 0.5 mL of 12.1M HCl. 52Mn was radiochemically isolated from thetarget solution (96% Ethanol, 0.12M HCl) by loading the activity onto approximately 150 mgof AG­1x8 strong anion exchange resin, followed by rinsing. 52Mn was eluted in 1 mL of 6MHCl, before repeating the purification with two additional separation cycles. The final productwas eluted in approximately 500 µL of 0.1M HCl. DOTA labeling was performed at pH 4using 0.25M pH 4.5 NaOAc to buffer the activity.ResultsAverage end of bombardment 52Mn yield was 0.14 ± 0.05 mCi/µAh (n=4). Radionuclidicpurity was measured to be greater than 99% by high­purity germanium analysis. Targetetching resulted in approximately 450 mg of chromium metal dissolution. An averageradiochemical separation yield of 72 ± 17% (n=2) has been observed. Total chromium mass inthe separated product was measured to be 1.1 ± 0.1 µg (n=1) by microwave plasma atomicemission spectrometry, corresponding to an overall separation factor of approximately 1.6 x105. DOTA chelation of 52Mn was found to be complete after one hour at room temperature,resulting in a measured effective specific activity of 0.05 Ci/µmol (n=1).ConclusionsProduction, separation, and chelation of 52Mn have been demonstrated with very simpletargetry and chemistry. These methods significantly improve over previous techniques [2­3] byimproving Cr target purity from 99.95% to 99.999% and by allowing for a trap­and­releasechromatographic separation. With such an approach, specific activities have been increasedand the 52Mn production process can be automated to reduce radiation dose to personnel.These developments will allow for rapid translation into imaging applications.This work was supported by the NIH Radiological Sciences Training Grant, the DOE (DE­FG02­12ER41882), and the NCI (5 T32 Ca009206­34).References[1] CM Lewis, SA Graves, et al., Theranostics, 5(3): 227­239, 2015.[2] S Lahiri, et al., Anal Chem, 78: 7517–21, 2006.[3] GJ Topping, et al., Med Phys, 40: 042502, 2013.TABLE TITLE:Trace Metal Analysis of Mn52 ProductTrace Metal Analysis of Mn52 ProductElement Mass (µg, ±10%)Cr 1.07Mn 0.11Fe 0.19Co 0.00Ni 0.00Cu 0.14Zn 3.30Table 1: Trace metal analysis by microwave plasma atomic emission spectrometry ofthe radiochemically separated Mn52 product.(No Image Selected)

Optimized 52Mn Production for Longlived PET Applications

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Optimized <sup>52</sup>Mn Production for Longlived PET Applications

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