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588 results on '"Lapi, Suzanne E."'

1. Quantitative Imaging of $^{55}\text{Co}$ and $^{18}\text{F}$-Labeled Tracers in a Single 'Multiplexed' PET Imaging Session

Author

Zou, Sarah J, Lim, Irene, Foster, Jackson W, Chinn, Garry, Houson, Hailey A, Lapi, Suzanne E., Rao, Jianghong, and Levin, Craig S

Subjects
Physics - Medical Physics
Abstract

In this study, we explore the use of Co-55 as a radioisotope for multiplexed PET (mPET) by utilizing its emission of a prompt gamma-ray in cascade with a positron during decay. We leverage the prompt-gamma signal to generate triple coincidences for a Co-55-labeled tracer, allowing us to distinguish it from a tracer labeled with a pure positron emitter, such as F-18. By employing triple versus double coincidence detection and signal processing methodology, we successfully separate the Co-55 signal from that of F-18. Phantom studies were conducted to establish the correlation between Co-55 double and triple coincidence counts and Co-55 activity. Additionally, we demonstrate the potential for quantifying hot spots within a warm background produced by both Co-55 and F-18 signals in a single PET scan. Finally, we showcase the ability to simultaneously image two tracers in vivo in a single PET session with mouse models of cancer., Comment: 5 pages, 4 figures, submitted IEEE ISBI 2025; v2: clarification on unstable Co-55-labeled antibody

Published
2024

3. Evaluating the immunologically “cold” tumor microenvironment after treatment with immune checkpoint inhibitors utilizing PET imaging of CD4 + and CD8 + T cells in breast cancer mouse models

Author

Lu, Yun, Houson, Hailey A., Gallegos, Carlos A., Mascioni, Alessandro, Jia, Fang, Aivazian, Argin, Song, Patrick N., Lynch, Shannon E., Napier, Tiara S., Mansur, Ameer, Larimer, Benjamin M., Lapi, Suzanne E., Hanker, Ariella B., and Sorace, Anna G.

Published
2024
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5. Antigen-dependent inducible T cell reporter system for PET imaging of breast cancer and glioblastoma

Author

Shin, Jaehoon, Parker, Matthew FL, Zhu, Iowis, Alanizi, Aryn, Rodriguez, Carlos I, Liu, Raymond, Watchmaker, Payal B, Kalita, Mausam, Blecha, Joseph, Luu, Justin, Wright, Brian, Lapi, Suzanne E, Flavell, Robert R, Okada, Hideho, Tlsty, Thea D, Roybal, Kole T, and Wilson, David M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Breast Cancer, Cancer, Biomedical Imaging, Biotechnology, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Animals, Humans, Female, Glioblastoma, T-Lymphocytes, Breast Neoplasms, Cell Line, Tumor, Positron-Emission Tomography, Genes, Reporter, SNIPR, CAR T, PET, reporter, cancer antigens, Clinical Sciences, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

For the past several decades, chimeric antigen receptor T-cell therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Methods: Using synthetic biology, we engineered T cells with a chimeric receptor synthetic intramembrane proteolysis receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette on recognition of specific tumor markers. We then applied a SNIPR-based PET reporter system to 2 cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors, respectively. Results: Antigen-specific reporter induction of the SNIPR PET T cells was confirmed in vitro using green fluorescent protein fluorescence, luciferase luminescence, and the HSV-TK PET reporter with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG). T cells associated with their target antigens were successfully imaged using PET in dual-xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII- animal models, with more than 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. Conclusion: The main innovation found in this work was PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.

Published
2023

10. Production and regulatory issues for theranostics

Author

Giammarile, Francesco, Paez, Diana, Zimmermann, Richard, Cutler, Cathy S, Jalilian, Amirreza, Korde, Aruna, Knoll, Peter, Ayati, Nayyereh, Lewis, Jason S, Lapi, Suzanne E, Delgado Bolton, Roberto C, Kunikowska, Jolanta, Estrada Lobato, Enrique, Urbain, Jean-Luc, Holmberg, Ola, Abdel-Wahab, May, and Scott, Andrew M

Published
2024
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12. Trends in nuclear medicine and the radiopharmaceutical sciences in oncology: workforce challenges and training in the age of theranostics

Author

Scott, Andrew M, Zeglis, Brian M, Lapi, Suzanne E, Scott, Peter J H, Windhorst, Albert D, Abdel-Wahab, May, Giammarile, Francesco, Paez, Diana, Jalilian, Amirreza, Knoll, Peter, Korde, Aruna, Vichare, Shrikant, Ayati, Nayyereh, Lee, Sze Ting, Lyashchenko, Serge K, Zhang, Jingjing, Urbain, Jean Luc, and Lewis, Jason S

Published
2024
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13. Antigen-dependent inducible T cell reporter system for PET imaging of breast cancer and glioblastoma

Author

Shin, Jaehoon, Parker, Matthew FL, Zhu, Iowis, Alanizi, Aryn, Rodriguez, Carlos I, Liu, Raymond, Watchmaker, Payal B, Kalita, Mausam, Blecha, Joseph, Luu, Justin, Wright, Brian, Lapi, Suzanne E, Flavell, Robert R, Okada, Hideho, Tlsty, Thea D, Roybal, Kole T, and Wilson, David M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Genetics, Biomedical Imaging, Biotechnology, Neurosciences, Breast Cancer, Cancer, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies
Abstract

Abstract: For the past several decades, chimeric antigen receptor T cell (CAR T) therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Using synthetic biology, we engineered T cells with a chimeric receptor SyNthetic Intramembrane Proteolysis Receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette upon recognition of specific tumor markers. We then applied a SNIPR-based positron emission tomography (PET) reporter system to two cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors respectively. Antigen-specific reporter induction of the SNIPR-PET T cells was confirmed in vitro using GFP fluorescence, luciferase luminescence, and the HSV-TK PET reporter with [18F]FHBG. T cells associated with their target antigens were successfully imaged using PET in dual xenograft HER2+/HER2- and EGFRvIII+/EGFRvIII-animal models, with > 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. The main innovation described is therefore PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression.

Published
2022

24. Development of 52Mn Labeled Trastuzumab for Extended Time Point PET Imaging of HER2.

Author

Omweri, James M., Saini, Shefali, Houson, Hailey A., Tekin, Volkan, Pyles, Jennifer M., Parker, Candace C., and Lapi, Suzanne E.

Subjects
POSITRON emission tomography, BISPECIFIC antibodies, RADIOCHEMICAL purification, BLOOD circulation, COMPUTED tomography
Abstract

Purpose: Due to their long circulation time in the blood, monoclonal antibodies (mAbs) such as trastuzumab, are usually radiolabeled with long-lived positron emitters for the development of agents for Positron Emission Tomography (PET) imaging. Manganese-52 (52Mn, t1/2 = 5.6 d, β+ = 29.6%, E(βave) = 242 keV) is suitable for imaging at longer time points providing a complementary technique to Zirconium-89 (89Zr, t1/2 = 3.3 d, β+ = 22.7%, E(βave) = 396 keV)) because of its long half-life and low positron energy. To exploit these properties, we aimed to investigate suitable bifunctional chelators that could be readily conjugated to antibodies and labeled with 52Mn under mild conditions using trastuzumab as a proof-of-concept. Procedures: Trastuzumab was incubated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), 1-Oxa-4,7,10-tetraazacyclododecane-5-S-(4-isothiocyantobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A), and 3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA) at a tenfold molar excess. The immunoconjugates were purified, combined with [52Mn]MnCl2 at different ratios, and the labeling efficiency was assessed by iTLC. The immunoreactive fraction of the radiocomplex was determined through a Lindmo assay. Cell studies were conducted in HER2 + (BT474) and HER2- (MDA-MB-468) cell lines followed by in vivo studies. Results: Trastuzumab-Oxo-DO3A was labeled within 30 min at 37 °C with a radiochemical yield (RCY) of 90 ± 1.5% and with the highest specific activity of the chelators investigated of 16.64 MBq/nmol. The labeled compound was purified with a resulting radiochemical purity of > 98% and retained a 67 ± 1.2% immunoreactivity. DOTA and PCTA immunoconjugates resulted in < 50 ± 2.5% (RCY) with similar specific activity. Mouse serum stability studies of [52Mn]Mn-Oxo-DO3A-trastuzumab showed 95% intact complex for over 5 days. Cell uptake studies showed higher uptake in HER2 + (12.51 ± 0.83% /mg) cells compared to HER2- (0.85 ± 0.10%/mg) cells. PET images of mice bearing BT474 tumors showed high tumor uptake that was consistent with the biodistribution (42.02 ± 2.16%ID/g, 14 d) compared to MDA-MB-468 tumors (2.20 ± 0.80%ID/g, 14 d). Additionally, both models exhibited low bone uptake of < 1% ID/g. Conclusion: The bifunctional chelator p-SCN-Bn-Oxo-DO3A is promising for the development of 52Mn radiopharmaceuticals as it was easily conjugated, radiolabeled at mild conditions, and illustrated stability for a prolonged duration both in vitro and in vivo. High-quality PET/CT images of [52Mn]Mn-Oxo-DO3A-trastuzumab were obtained 14 d post-injection. This study illustrates the potential of [52Mn]Mn-Oxo-DO3A for the evaluation of antibodies using PET imaging. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Molecular design for sub-micromolar enzyme-instructed self-assembly (EISA).

Author

Liu, Qihui, Ntim, Thomas, Wu, Zhiyuan, Houson, Hailey A., Lapi, Suzanne E., and Lindsey, Jonathan S.

Subjects
ARYL group, LIFE sciences, POLYETHYLENE glycol, FLUORESCENCE spectroscopy, PEPTIDES, ALKALINE phosphatase
Abstract

Enzyme-instructed self-assembly (EISA) has been explored for many applications in the life sciences including imaging and therapeutics. To date, use of the strategy is limited by the relatively high concentration – often in the mM regime – required for assembly. Here, a porphyrin–peptide conjugate (1) was designed as a water-soluble, EISA substrate. Compound 1 is built around a trans-AB porphyrin chassis that is equipped with a monodisperse 1 kDa polyethylene glycol (PEG) linker (a surrogate for a potential targeting agent) and an enzymatically triggerable self-assembly motif. The latter is comprised of two identical self-assembly peptides (also known as hydrogelators) attached to the 2,6-positions of an aryl group. The peptides have sequence GffY and in protected form contain tyrosine as an O-phosphoester GffY(p). Treatment of 1 with alkaline phosphatase (ALP) gave rise to the self-assembly (or aggregation) process as characterized by absorption spectroscopy. A control compound without the phosphoester trigger was synthesized and examined for the self-assembly process using fluorescence and absorption spectroscopy. A concentration-dependent study showed that at 10 nM approximately 50% of porphyrin–peptide conjugate was in the aggregated form. The nanomolar assembly suggests possible applications of EISA substrates in chemotherapy, although a further decrease in concentration to the picomolar regime may be required for use in targeted molecular radiotherapy, where very low mass dosing is typical. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Production and Separation of 7be for Use in an Ion Source

Author

Severin, Gregory, primary, Satija, Samridhi, additional, Domnanich, Katharina A., additional, Sumithrarachchi, Chandana, additional, Liu, Yuan, additional, Cingoranelli, Shelbie J., additional, Saini, Shefali, additional, Chaple, Ivis, additional, and Lapi, Suzanne E., additional

Published
2024
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