The goal of this study was to utilize a multimodal magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging approach to assess the local innate immune response in skeletal muscle and draining lymph node following vaccination in rats using two different vaccine platforms (AS01 adjuvanted protein and lipid nanoparticle (LNP) encapsulated Self-Amplifying mRNA (SAM)). MRI and 18FDG PET imaging were performed temporally at baseline, 4, 24, 48, and 72 hr post Prime and Prime-Boost vaccination in hindlimb with Cytomegalovirus (CMV) gB and pentamer proteins formulated with AS01, LNP encapsulated CMV gB protein-encoding SAM (CMV SAM), AS01 or with LNP carrier controls. Both CMV AS01 and CMV SAM resulted in a rapid MRI and PET signal enhancement in hindlimb muscles and draining popliteal lymph node reflecting innate and possibly adaptive immune response. MRI signal enhancement and total 18FDG uptake observed in the hindlimb was greater in the CMV SAM vs CMV AS01 group (↑2.3 – 4.3-fold in AUC) and the MRI signal enhancement peak and duration were temporally shifted right in the CMV SAM group following both Prime and Prime-Boost administration. While cytokine profiles were similar among groups, there was good temporal correlation only between IL-6, IL-13, and MRI/PET endpoints. Imaging mass cytometry was performed on lymph node sections at 72 hr post Prime and Prime-Boost vaccination to characterize the innate and adaptive immune cell signatures. Cell proximity analysis indicated that each follicular dendritic cell interacted with more follicular B cells in the CMV AS01 than in the CMV SAM group, supporting the stronger humoral immune response observed in the CMV AS01 group. A strong correlation between lymph node MRI T2 value and nearest-neighbor analysis of follicular dendritic cell and follicular B cells was observed (r=0.808, P<0.01). These data suggest that spatiotemporal imaging data together with AI/ML approaches may help establish whether in vivo imaging biomarkers can predict local and systemic immune responses following vaccination.

Abstract Purpose Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc-receptor (FcRn)-mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS modified equivalent, VIR-7831-WT in cynomolgus monkeys. Methods 89Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on respiratory tract, and a physiologically-based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values. Results SUVmean uptake in the pulmonary bronchi for 89Zr-VIR-7831 was statistically higher than 89Zr-VIR-7831-WT at Days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively), and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at Days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUVmean uptake ratio for both mAbs was 0.25 on Day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31, 0.55, respectively. Radiomics analysis showed VIR-7831 had mean centralized PET SUV distribution in lung and liver, indicating more uniform uptake than VIR-7831-WT. Conclusion The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89Zr label sheds light on the sites of antibody catabolism.

Purpose Sotrovimab (VIR-7831), a human IgG1κ monoclonal antibody (mAb), binds to a conserved epitope on the SARS-CoV-2 spike protein receptor binding domain (RBD). The Fc region of VIR-7831 contains an LS modification to promote neonatal Fc receptor (FcRn)–mediated recycling and extend its serum half-life. Here, we aimed to evaluate the impact of the LS modification on tissue biodistribution, by comparing VIR-7831 to its non-LS-modified equivalent, VIR-7831-WT, in cynomolgus monkeys. Methods 89 Zr-based PET/CT imaging of VIR-7831 and VIR-7831-WT was performed up to 14 days post injection. All major organs were analyzed for absolute concentration as well as tissue:blood ratios, with the focus on the respiratory tract, and a physiologically based pharmacokinetics (PBPK) model was used to evaluate the tissue biodistribution kinetics. Radiomics features were also extracted from the PET images and SUV values. Results SUV mean uptake in the pulmonary bronchi for 89 Zr-VIR-7831 was statistically higher than for 89 Zr-VIR-7831-WT at days 6 (3.43 ± 0.55 and 2.59 ± 0.38, respectively) and 10 (2.66 ± 0.32 and 2.15 ± 0.18, respectively), while the reverse was observed in the liver at days 6 (5.14 ± 0.80 and 8.63 ± 0.89, respectively), 10 (4.52 ± 0.59 and 7.73 ± 0.66, respectively), and 14 (4.95 ± 0.65 and 7.94 ± 0.54, respectively). Though the calculated terminal half-life was 21.3 ± 3.0 days for VIR-7831 and 16.5 ± 1.1 days for VIR-7831-WT, no consistent differences were observed in the tissue:blood ratios between the antibodies except in the liver. While the lung:blood SUV mean uptake ratio for both mAbs was 0.25 on day 3, the PBPK model predicted the total lung tissue and the interstitial space to serum ratio to be 0.31 and 0.55, respectively. Radiomics analysis showed VIR-7831 had mean-centralized PET SUV distribution in the lung and liver, indicating more uniform uptake than VIR-7831-WT. Conclusion The half-life extended VIR-7831 remained in circulation longer than VIR-7831-WT, consistent with enhanced FcRn binding, while the tissue:blood concentration ratios in most tissues for both drugs remained statistically indistinguishable throughout the course of the experiment. In the bronchiolar region, a higher concentration of 89 Zr-VIR-7831 was detected. The data also allow unparalleled insight into tissue distribution and elimination kinetics of mAbs that can guide future biologic drug discovery efforts, while the residualizing nature of the 89 Zr label sheds light on the sites of antibody catabolism.

Prostate cancer is the most common malignancy and leading cause of cancer deaths in men. Thus, the development of novel strategies for performing combined prostate cancer imaging and therapy methods is crucial and could have a significant impact on patient care. This current study aimed to design a multimodality nanoconjugate to be used for both PET and optical imaging and as a therapeutic radio/photo sensitizer and anti-angiogenesis agent. Initial characterization of this novel nanoconjugate was performed via HPLC, FTIR, TEM and DLS analyses. Pt@TiO2-SPHINX was further evaluated using fluorometric and radiochromatographic methods. Cytotoxicity, cell uptake and internalization were also investigated as well as therapy with photodynamic/radio therapy combinations. Both nanoparticles and nanoconjugates were robustly synthesized according to literature methods. Radiochemistry and cell culture assays showed high 89Zr radiolabeling efficiency with sufficient stability for studies at later time points. Pt@TiO2-SPHINX was shown to target prostate cancer cells (PC3 and LNCaP), and was non-toxic to normal prostate cells (RWPE-1). This finding was supported by the WST-8 assay and AFM images. The uptake of the compound in prostate cancer cells is significantly higher than prostate normal cells and according to ELISA results, Pt@TiO2-SPHINX can increase anti-angiogenic VEGFA165b. Additionally, Pt@TiO2-SPHINX dramatically decreased the cell viability of prostate cancer cells when photodynamic and radio therapy were performed at the same time. In vitro results are promising for future studies of Pt@TiO2-SPHINX as a PET imaging agent and anti-angiogenic radio sensitizer.

The authors regret not including the full funding support for this publication. The Funding/Support paragraph should be corrected as follows: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health (NCATS NIH) under award number UL1TR001417 and by American Cancer Society under the award number ACS-IRG -18-162-59-IRG. The content is the sole responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors would like to apologise for any inconvenience caused. Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatmentSurgeryVol. 167Issue 1PreviewNeuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. Full-Text PDF

Elevated blood sera concentrations of perfluorinated and polyfluorinated alkyl substances (PFAS) are associated with many adverse human health effects, including lower birth weight children. Yet the biodistribution of PFAS between mother and fetus remains unknown. The first comparative uptake and in vivo biodistribution study of "long-chain" and "short-chain" PFAS was performed on healthy, pregnant mice via two routes of administration, tail vein injection and oral gavage ingestion. Two F-18 radiolabeled PFAS, [F-18]PFOA (C8) and [F-18]PFHxA (C6), were administered to pregnant mice, and real-time distribution was investigated by dynamic positron emission tomography (PET). Post imaging, the biodistribution of the radio-labeled PFAS compounds were quantified by ex vivo gamma counting. Imaging following tail vein administration showed rapid uptake of both [F-18]PFAS in placentae followed by transport into fetuses. Oral gavage showed a slower uptake but still exhibited transport across the placenta. PFAS uptake was found in all tissues examined, with the highest uptake being exhibited in the blood for both [F-18]C8 and [F-18]C6 via tail vein and the lungs via oral gavage. These initial results provide insight into the link between PFAS exposure in pregnant mammals and offspring health.

Vitamin H (biotin) is delivered to the fetus transplacentally by an active biotin-transport mechanism and is critical for fetal development. Our objective was to develop a comprehensive MRI technique for mapping biotin transporter activity in the murine placenta. Visualization of transporter activity can employ MRI’s unique T 2 *-dependent signal ‘off-switch’, which is triggered by transporter mediated aggregation of biotinylated contrast agent (b-BSA-Gd-DTPA). MRI data were collected from pregnant mice after administration of b-BSA-Gd-DTPA and analyzed using a new sub-voxel biophysical signal model. Validation experiments included competition with native biotin, comparative tests using PET, histology, and ICPMS. MRI signal was governed by binding, aggregation, and clearance of biotin (confirmed by histology). Signal dynamics reflected the placenta’s perfusion pattern modulated by biotin transporter activity and trophoblast mediated retention, and were in congruence with a three-compartment sub-voxel model. Pre-saturation of the transporters with free biotin suppressed b-BSA-Gd-DTPA uptake. The results were confirmed by PET, histology and ICPMS. The presented MRI-based platform allows to track activity of essential molecular transporters in the placenta, reflecting a transporter-mediated uptake, followed by retention and aggregation, and recycling associated with the large b-BSA-Gd-DTPA conjugate. The presented DCE-MRI technique can furthermore be used to map and characterize microstructural compartmentation and transporter activity without exposing the fetus to contrast media.

72 Objectives: Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer related death in women. Significantly, therapy targeting receptors overexpressed in breast cancer has led to successful treatment options for many women. In particular, treatments targeting the Human Epidermal Growth Factor Receptor 2 (HER2) such as Trastuzumab, Pertuzumab and T-DM1 have improved patient outcomes. As patient response relies heavily on the expression of HER2, the development of imaging strategies for HER2 and other receptors to aid in patient selection for targeted therapies is an urgent need. One potential solution is the use of peptides as radiolabeled imaging agents. Methods: HER2 binding peptides were designed with the conjugation of a DOTA chelator to bind 68Ga for PET imaging. A modified peptide reported by Huawei et al. from Journal of Fluorescence, (DOTA-Bn-SCN)-PEG2-GSGKCCYSL, was radiolabeled with 68Ga at 95 °C for 12 min at a pH of 4.5.1 The combination of labeled peptide and phosporamidon or PA (an enzyme inhibitor to prevent degradation described by Nock et al. in Journal of Nuclear Medicine) was added to three cell-lines: HER2-negative MDA-MB-231, HER2 positive SKBR3, and HER2 positive BT474 to confirm specificity and uptake of the designed peptide. Cells were plated on 24-well plates (8 per cell line) and incubated at 37 °C for 15 min in the presence of 300nM of peptide and 200nM of PA in 1mL of media per well. Cells were washed with ice-cold PBS and removed with 0.5M NaOH. Cells were collected and counted on a HIDEX Automatic Gamma Counter and the %uptake/mg of radioactivity/peptide per protein was determined. Results: Peptide radiolabeling resulted in greater than 98% radiochemical yields, with a specific activity of 49Ci/g, showing an efficient radiolabeling that is favorable for cell-studies and future investigations. Cell-studies showed that HER2 positive SKBR3 cells had significantly more %uptake/mg of the radiotracer (0.020±0.006s.e.) similar to HER2 positive BT474 cells (0.026±.008s.e.) compared to the non-HER2 expressing MDA-MB-231 (0.010±.004s.e.). All samples had n=16 and analysis was done using a one-way ANOVA with a Tukey’s post-hoc test. Conclusions: These preliminary studies show promising results for the development of Targeted peptides for HER2 imaging. Other peptide sequences are under investigation. With these preliminary results, tumor xenograft mice models will be planned to look at the in vivo stability, binding affinity, and biodistribution. Overall, we aim to optimize our peptide conjugates to fine tune pharmacokinetics and PET imaging attributes.Acknowledgements: I would like to thank the Lapi Lab and the Cyclotron Crew for their constant support and help. I would also like to thank UAB Radiology for funding and opportunity to do my research.

Pulmonary carcinoids are a type of neuroendocrine tumor (NET) accounting for 1–2% of lung cancer cases. Currently, Positron Emission Tomography (PET)/CT based on the radiolabeled sugar analogue [18F]-FDG is used to diagnose and stage pulmonary carcinoids, but is suboptimal due to low metabolic activity in these tumors. A new technique for pulmonary carcinoid imaging, using PET/CT with radiolabeled somatostatin analogs that specifically target somatostatin receptor subtype 2 (SSTR2), is becoming more standard, as many tumors overexpress SSTR2. However, pulmonary carcinoid patients with diminished SSTR2 expression are not eligible for this imaging or any type of SSTR2-specific treatment. We have found that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 in pulmonary carcinoid cell lines. In this study, we used a non-cytotoxic dose of HDAC inhibitors to induce pulmonary carcinoid SSTR2 expression in which we confirmed in vitro and in vivo. A non-cytotoxic dose of the HDAC inhibitors: thailandepsin A (TDP-A), romidepsin (FK228), suberoylanilide hydroxamic acid (SAHA), AB3, and valproic acid (VPA) were administered to promote SSTR2 expression in pulmonary carcinoid cell lines and xenografts. This SSTR2 upregulation technique using HDAC inhibitors could enhance radiolabeled somatostatin analog-based imaging and the development of potential targeted treatments for pulmonary carcinoid patients with marginal or diminished SSTR2 expression.

Molecular probes targeting bacteria provide opportunities to target bacterial infections in vivo for both imaging and therapy. In the current study, we report the development of positron emission tomography (PET) probes for imaging of live bacterial infection based on the small molecules HLys-DOTA, a polycationic peptide synthesized as the D-isomer (RYWVAWRNRG) conjugated to 1, 4, 7, 10-tetraazacyclododecane-N′,N″,N‴,N-tetraacetic acid (DOTA) and AB1-HLys-DOTA, which includes an unnatural amino acid AB1 that preferentially binds to bacteria membrane lipids with amine groups via formation of iminoboronates. HLys-DOTA and AB1-HLys-DOTA peptides were radiolabeled with 64Cu and investigated as PET imaging agents to track bacterial infection in vitro and in intramuscularly infected (IM) mice models. Cell uptake studies at 37°C in Staphylococcus aureus (SA) show higher uptake of 64Cu-AB1-HLys-DOTA; 98.47 ± 3.54% vs 64Cu-HLys-DOTA; 39.12 ± 3.27% at 24 h. Standard uptake values (SUV) analysis of the PET images resulted in mean SUV of 0.70 ± 0.08, 0.49 ± 0.04, and 0.31 ± 0.01 for 64Cu-AB1-HLys-DOTA and 0.17 ± 0.06, 0.16 ± 0.02, and 0.13 ± 0.01 for 64Cu-HLys-DOTA at 1, 4, and 24 h post injection, respectively, in the infected muscles. Similarly, in the biodistribution studies, dose uptake in the infected muscles was 4 times higher in the targeted 64Cu-AB1-HLys-DOTA group than in the 64Cu-HLys-DOTA group and 2‐3 times higher than in the PBS control group at 1, 4, and 24 h post injection. 64Cu-AB1-HLys-DOTA was able to distinguish between SA-infected muscle and Pseudomonas aeruginosa (PA) infected muscle with lower mean SUV of 0.28 ± 0.10 at 1 h post injection. This illustrates the utility of the AB1 covalently targeting group in synergy with the HLys peptide, which noncovalently binds to bacterial membranes. These results suggest that 64Cu-labeled AB1-HLys-DOTA peptide could be used as an imaging probe for detection of bacterial infection in vivo with specificity for Gram-positive bacteria.

Background: The success of human epidermal growth factor receptor 2 (HER2)-targeted therapy depends on accurate characterization of HER2 expression, but current methods available have several limitations. This study aims to investigate the feasibility of [Zr-89]pertuzumab imaging to monitor early response to Ado-trastuzumab emtansine (T-DM1) therapy in mice bearing xenografts of HER2-positive breast cancer (BCa). Materials and Methods: Pertuzumab was conjugated to DFO-Bz-NCS and labeled with Zr-89. Mice bearing BT-474 tumors were imaged with [Zr-89]pertuzumab and [F-18]FDG before and after T-DM1 therapy. Results: Pertuzumab was successfully labeled with Zr-89 with a specific activity of 0.740 MBq/mu g. Overall [F-18]FDG images showed poor delineation of tumors. Using [F-18]FDG-PET to measure tumor volume, the volume remained unchanged from 107.6 +/- 20.7 mm(3) before treatment to 89.87 +/- 66.55 mm(3) after treatment. In contrast, [Zr-89]pertuzumab images showed good delineation of HER2-positive tumors, allowing accurate detection of changes in tumor volume (from 243.80 +/- 40.91 mm(3) before treatment to 78.4 +/- 40.43 mm(3) after treatment). Conclusion: [Zr-89]pertuzumab may be an imaging probe for monitoring the response of HER2-positive BCa patients to T-DM1 therapy.

265 Objectives: Pulmonary fibrosis (PF) involves scarring of the lung tissue. This scarring is essentially buildup of the deposition of extracellular matrices such as collagen, elastin and glycoproteins. Over time this buildup results in decreased pulmonary function and usually proves to be a fatal condition. Causes of PF are wide ranging but most cases are idiopathic, having no known cause. In this study, we aimed to assess the use of a novel 89Zr PET imaging agent, [89Zr]JLB-01, to monitor the progression of the disease on a weekly basis in mice whose lungs were injured with bleomycin, an agent known to induce PF in animal models. Methods: D-Hphe-AMBH-DFO was synthesized in 6 steps starting with N-boc-homo-phenylalanine and 4-aminobenzoic acid. D-Hphe-AMBH-DFO was dissolved into DMSO and incubated in a solution with 89Zr at a pH of 7.2 in HEPES buffer to yield the desired compound of [89Zr]JLB-01. Specific activity was calculated based off the starting compound and radiochemical purity was determined via instant thin layer chromatography. At T0 (week 1), a group of mice (n=6/group) were injured accordingly, with either bleomycin or saline, injected with ~225 μCi of [89Zr]JLB-01 via tail vein, then imaged at 1 h and 4 h post injection. Each group was studied on subsequent days. Four weeks post injury, 3 mice per group were sacrificed post PET imaging for biodistribution purposes. The remaining mice were injected, imaged and sacrificed during week 5. Results: Synthesis of the precursor D-Hphe-AMBH-DFO proved challenging with the lowest yielding step being the coupling between the hydrazide and the carboxylic acid of 4-aminobenzoic acid (scheme not shown). The final synthetic yield over 6 steps was ~5% For radiolabeling purposes, [89Zr]JLB-01, was easily synthesized within 15 min at 95oC resulting in >95% purity, and acceptable specific activity at 4 mCi/μg. The preliminary biodistribution studies showed that at week 4 (the week expected to have the most fibrotic tissue), 3.4 + 0.1% ID/g was observed in the bleomycin injured lungs vs. just 1.0 + 0.2 % ID/g in the saline injured lungs (p = .0007). At week 5, when the lungs were expected to start recovering from the injury, the uptake of [89Zr]JLB-01 was just 0.6 + 0.1 %ID/g in the bleomycin injured group vs. 0.4 + 0.3 %ID/g in the saline injured group. Conclusion: The synthesis of the radiolabeling precursor, D-Hphe-AMBH-DFO, was short and low yielding however radiolabeling proved to be high yielding with good radiochemical purity and specific activity. Overall the compound [89Zr]JLB-01 showed that it is possible to study the progression of the development of pulmonary fibrosis in mice injured with bleomycin.

An increasing interest in zirconium-89 (Zr-89) can be attributed to the isotope's half-life which is compatible with antibody imaging using positron emission tomography (PET). The goal of this work was to develop an efficient means of production for Zr-89 that provides this isotope with high radionuclidic purity and specific activity. We investigated the irradiation of yttrium sputtered niobium coins and compared the yields and separation efficiency to solid yttrium coins. The sputtered coins were irradiated with an incident beam energy of 17.5 MeV or 17.8 MeV providing a degraded transmitted energy through an aluminum degrader of 12.5 MeV or 12.8 MeV, respectively, with various currents to determine optimal cyclotron conditions for Zr-89 production. Dissolution of the solid yttrium coin took 2 h with 50 mL of 2 M HC1 and dissolution of the sputtered coin took 15-30 min with 4 mL of 2 M HCI. During the separation of Zr-89 from the solid yttrium coins, 77.9 +/- 11.2% of the activity was eluted off in an average of 73 mL of 1 M oxalic acid whereas for the sputtered coins, 91 +/- 6% was eluted off in an average of 1.2 mL of 1 M oxalic add with 100% radionuclidic purity. The effective specific activity determined via DFO-SCN titration from the sputtered coins was 108 7 mCi/pmol as compared to 20.3 mCi/pmol for the solid yttrium coin production. ICP-MS analysis of the yttrium coin and the sputtered coins showed 99.99% yttrium removed with 178 lag of yttrium in the final solution and 99.93-100% of yttrium removed with remaining range of 0-42 lag of yttrium in the final solution, respectively. The specific activity calculated for the solid coin and 3 different sputtered coins using the concentration of Zr found via ICP-MS was 140 +/- 2 mCi/pmol, 300 30 mCi/ punol, 410 +/- 60 mCi/pmol and 1719 5 mCi/pmol, respectively. Labeling yields of the Zr-89 produced via sputtered targets for Zr-89-DFO-trastuzumab were >98%. Overall, these results show the irradiation of yttrium sputtered niobium coins is a highly effective means for the production of Zr-89. (C) 2017 Elsevier Inc. All rights reserved.

An increasing interest in zirconium-89 (89Zr) can be attributed to the isotope's half-life which is compatible with antibody imaging using positron emission tomography (PET). The goal of this work was to develop an efficient means of production for 89Zr that provides this isotope with high radionuclidic purity and specific activity. We investigated the irradiation of yttrium sputtered niobium coins and compared the yields and separation efficiency to solid yttrium coins. The sputtered coins were irradiated with an incident beam energy of 17.5MeV or 17.8MeV providing a degraded transmitted energy through an aluminum degrader of 12.5MeV or 12.8MeV, respectively, with various currents to determine optimal cyclotron conditions for 89Zr production. Dissolution of the solid yttrium coin took 2h with 50mL of 2M HCl and dissolution of the sputtered coin took 15-30min with 4mL of 2M HCl. During the separation of 89Zr from the solid yttrium coins, 77.9 ± 11.2% of the activity was eluted off in an average of 7.3mL of 1M oxalic acid whereas for the sputtered coins, 91 ± 6% was eluted off in an average of 1.2mL of 1M oxalic acid with 100% radionuclidic purity. The effective specific activity determined via DFO-SCN titration from the sputtered coins was 108±7mCi/μmol as compared to 20.3mCi/μmol for the solid yttrium coin production. ICP-MS analysis of the yttrium coin and the sputtered coins showed 99.99% yttrium removed with 178μg of yttrium in the final solution and 99.93-100% of yttrium removed with remaining range of 0-42μg of yttrium in the final solution, respectively. The specific activity calculated for the solid coin and 3 different sputtered coins using the concentration of Zr found via ICP-MS was 140±2mCi/μmol, 300±30mCi/μmol, 410±60mCi/μmol and 1719±5mCi/μmol, respectively. Labeling yields of the 89Zr produced via sputtered targets for 89Zr- DFO-trastuzumab were >98%. Overall, these results show the irradiation of yttrium sputtered niobium coins is a highly effective means for the production of 89Zr.