Introduction 52Mn (t½ =5.59 d, β+ = 29.6%, Eβmax = 0.58 MeV) has great potential as a long lived PET isotope for use in cell tracking studies, observation of immunologic response to disease states, or as an alternative to manganese-based MRI contrast agents. Its favorable max positron energy leads to superb imaging resolution, comparable to that of 18F.[1] Manganese is naturally taken up by cells via a multitude of pathways including the divalent metal transporter (DMT1), ZIP8, transferrin receptors (TfR), store-operated Ca2+ channels (SOC-Ca2+), and ionotropic glutamate receptor Ca2+ channels (GluR).[2] These natural transport mechanisms make 52Mn an attractive isotope for applications necessitating non-perturbative cell uptake. In particular, cell tracking is critical to the development and translation of stem cell therapies in regenerative medicine. Alternative-ly, 52Mn could be used in immunotherapy techniques such as adoptive cellular therapy (ACT) to evaluate the ability of external immune cells to reach their intended target. Material and Methods 52Mn was produced by natCr(p,x)52Mn using 16 MeV protons. The average thick target production yield was 0.23 mCi/µA-h with less than 0.25% co-production of 54Mn. Small amounts of 51Cr were observed in the target, but were absent from the radiochemically separated product. Target construction consisted of a water jet cooled chromium disc (3/4” diameter, 0.4” thick). Targets were purchased from Kamis Inc, and are 99.95% pure. Targets withstood beam currents of 30 µA with no visible aberration. Chromium targets were etched by concentrated HCl following bombardment. Mn2+ ions were extracted from 9M HCl to 0.8M trioctylamine in cyclohexane leaving the bulk chromium in the aqueous phase. After isolating the organic phase, 0.001M NH4OH was used to back-extract the Mn2+ ions to aqueous phase. This purification cycle was conducted a total of three times for each 52Mn production. Results and Conclusion For a starting bulk chromium mass of 456 ± 1 mg, a post-separation chromium mass of 5.35 ± 0.04 ng was measured by microwave plasma atomic emission spectrometry (MP-AES). This mass reduction corresponds to an average separation factor of 440 for a single purification cycle. Each purification cycle had a 52Mn recovery efficiency of 73 ± 7 % (n = 6), resulting in an overall separation efficiency of approximately 35 %. These efficiencies and separation factors agree reasonably well with the work conducted by Lahiri et. al.[3] Prior to use, the product was passed through a C-18 Sep-Pak to remove any residual organic phase. After four target irradiations and etchings, some pitting became noticeable on the target face. These have not yet compromised the o-ring seal with the target deplater, but it is possible that target replacement after every 6–9 52Mn productions will be necessary moving forward. Following the successful separation of 52Mn from chromium, in vitro experiments were conducted to demonstrate the uptake of 52Mn by human stem cells and mouse tumor cells. A linear uptake response was observed as a function of the amount of activity exposed to the cells for both cell models. These experiments have shown great promise for 52Mn as a long-lived PET isotope in cell tracking studies. Details will be presented.

Introduction 52Mn (t½ =5.59 d, β+ = 29.6%, Eβmax = 0.58 MeV) has great potential as a long lived PET isotope for use in cell tracking studies, observation of immunologic response to disease states, or as an alternative to manganese-based MRI contrast agents. Its favorable max positron energy leads to superb imaging resolution, comparable to that of 18F.[1] Manganese is naturally taken up by cells via a multitude of pathways including the divalent metal transporter (DMT1), ZIP8, transferrin receptors (TfR), store-operated Ca2+ channels (SOC-Ca2+), and ionotropic glutamate receptor Ca2+ channels (GluR).[2] These natural transport mechanisms make 52Mn an attractive isotope for applications necessitating non-perturbative cell uptake. In particular, cell tracking is critical to the development and translation of stem cell therapies in regenerative medicine. Alternative-ly, 52Mn could be used in immunotherapy techniques such as adoptive cellular therapy (ACT) to evaluate the ability of external immune cells to reach their intended target. Material and Methods 52Mn was produced by natCr(p,x)52Mn using 16 MeV protons. The average thick target production yield was 0.23 mCi/µA-h with less than 0.25% co-production of 54Mn. Small amounts of 51Cr were observed in the target, but were absent from the radiochemically separated product. Target construction consisted of a water jet cooled chromium disc (3/4” diameter, 0.4” thick). Targets were purchased from Kamis Inc, and are 99.95% pure. Targets withstood beam currents of 30 µA with no visible aberration. Chromium targets were etched by concentrated HCl following bombardment. Mn2+ ions were extracted from 9M HCl to 0.8M trioctylamine in cyclohexane leaving the bulk chromium in the aqueous phase. After isolating the organic phase, 0.001M NH4OH was used to back-extract the Mn2+ ions to aqueous phase. This purification cycle was conducted a total of three times for each 52Mn production. Results and Conclusion For a starting bulk chromium mass of 456 ± 1 mg, a post-separation chromium mass of 5.35 ± 0.04 ng was measured by microwave plasma atomic emission spectrometry (MP-AES). This mass reduction corresponds to an average separation factor of 440 for a single purification cycle. Each purification cycle had a 52Mn recovery efficiency of 73 ± 7 % (n = 6), resulting in an overall separation efficiency of approximately 35 %. These efficiencies and separation factors agree reasonably well with the work conducted by Lahiri et. al.[3] Prior to use, the product was passed through a C-18 Sep-Pak to remove any residual organic phase. After four target irradiations and etchings, some pitting became noticeable on the target face. These have not yet compromised the o-ring seal with the target deplater, but it is possible that target replacement after every 6–9 52Mn productions will be necessary moving forward. Following the successful separation of 52Mn from chromium, in vitro experiments were conducted to demonstrate the uptake of 52Mn by human stem cells and mouse tumor cells. A linear uptake response was observed as a function of the amount of activity exposed to the cells for both cell models. These experiments have shown great promise for 52Mn as a long-lived PET isotope in cell tracking studies. Details will be presented.

In der vorliegenden Arbeit wurde mit Hilfe von Gefäßversuchen der Transfer von ausgewählten organischen (m-Kresol, Simazin, Lindan, Anthracen, Galaxolid) und anorganischen Umweltschadstoffen (As, Cd, Pb, Cr, Zn, Ni) aus dotiertem Substrat in Nutzpflanzen (Tomaten, Paprika) untersucht. Zum besseren Verständnis des Schadstofftransfers der organischen Verbindungen und als Möglichkeit einer kosten- und zeitsparenden Alternative zu den herkömmlichen Untersuchungsverfahren, wurden ergänzend in vivo – Experimente durchgeführt. Weitere Schwerpunkte der Arbeit waren Untersuchungen zur Schadstoffaufnahme durch Pflanzen in Abhängigkeit von der Substratkonzentration sowie der Vegetationsdauer. Ein weiterer Schwerpunkt der Arbeiten waren Studien über mögliche Einflüsse eines neuartigen Bodenverbesserungsmaterials auf die Schadstoffmobilität und Bioverfügbarkeit der oben genannten potentiellen Schadstoffe sowie die damit verbundene mögliche Aufnahme durch die Untersuchungspflanzen.

In der vorliegenden Arbeit wurde mit Hilfe von Gefäßversuchen der Transfer von ausgewählten organischen (m-Kresol, Simazin, Lindan, Anthracen, Galaxolid) und anorganischen Umweltschadstoffen (As, Cd, Pb, Cr, Zn, Ni) aus dotiertem Substrat in Nutzpflanzen (Tomaten, Paprika) untersucht. Zum besseren Verständnis des Schadstofftransfers der organischen Verbindungen und als Möglichkeit einer kosten- und zeitsparenden Alternative zu den herkömmlichen Untersuchungsverfahren, wurden ergänzend in vivo – Experimente durchgeführt. Weitere Schwerpunkte der Arbeit waren Untersuchungen zur Schadstoffaufnahme durch Pflanzen in Abhängigkeit von der Substratkonzentration sowie der Vegetationsdauer. Ein weiterer Schwerpunkt der Arbeiten waren Studien über mögliche Einflüsse eines neuartigen Bodenverbesserungsmaterials auf die Schadstoffmobilität und Bioverfügbarkeit der oben genannten potentiellen Schadstoffe sowie die damit verbundene mögliche Aufnahme durch die Untersuchungspflanzen.