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

2. 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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4. 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

9. 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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10. 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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15. 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

29. 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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32. 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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35. PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402

Author

Gimblet, Grayson R., Houson, Hailey A., Whitt, Jason, Reddy, Pratheek, Copland, John Al, Kenderian, Saad S., Szkudlinski, Mariusz W., Jaskula-Sztul, Renata, and Lapi, Suzanne E.

Abstract

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2= 78.4 h, β+= 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitroin stably transduced TSHR+ and wild-type TSHR– DTC cell lines. In vivoPET imaging was performed on Days 1–3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR– xenografts, along with ex vivobiodistribution on Day 3 postinjection. In vitrouptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P< 0.0001) and FTC133 (P< 0.01) cells than in TSHR– THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P< 0.0001) and TSHR+ FTC133 (P< 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivoPET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivobiodistribution confirmed a significant difference (P< 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133– (0.8 ± 0.1%ID/g) tumors. A significant difference (P< 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T– (0.8 ± 0.4%ID/g) tumors. The in vitroand in vivoaccumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Published
2024
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36. Improving the In Vivo Stability of [52Mn]Mn(II) Complexes with 18-Membered Macrocyclic Chelators for PET Imaging

Author

Harriswangler, Charlene, Omweri, James M., Saini, Shefali, Valencia, Laura, Esteban-Gómez, David, Ranga, Madalina, Guidolin, Nicol, Baranyai, Zsolt, Lapi, Suzanne E., and Platas-Iglesias, Carlos

Abstract

We report the [natMn/52Mn]Mn(II) complexes of the macrocyclic chelators PYAN [3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane] and CHXPYAN [(41R,42R,101R,102R)-3,5,9,11-tetraaza-1,7(2,6)-dipyridina-4,10(1,2)-dicyclohexanacyclododecaphane]. The X-ray crystal structures of Mn-PYAN and Mn-CHXPYAN evidence distorted octahedral geometries through coordination of the nitrogen atoms of the macrocycles. Cyclic voltammetry studies evidence reversible processes due to the Mn(II)/Mn(III) pair, indicating that the complexes are resistant to oxidation. CHXPYAN forms a more thermodynamically stable and kinetically inert Mn(II) complex than PYAN. Radiochemical studies with the radioactive isotope manganese-52 (52Mn, t1/2= 5.6 days) evidenced better radiochemical yields for CHXPYAN than for PYAN. Both [52Mn]Mn(II) complexes remained stable in mouse and human serum, so in vivo stability studies were carried out. Positron emission tomography/computed tomography scans and biodistribution assays indicated that [52Mn]Mn-PYAN has a distribution pattern similar to that of [52Mn]MnCl2, showing persistent radioactivity accumulation in the kidneys. Conversely, [52Mn]Mn-CHXPYAN remained stable in vivo, clearing quickly from the liver and kidneys.

Published
2024
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38. Titanium-45 (45 Ti) Radiochemistry and Applications in Molecular Imaging.

Author

Saini, Shefali and Lapi, Suzanne E.

Subjects
*RADIOCHEMISTRY, *POSITRON emission tomography, *RADIOISOTOPES, *NUCLEAR medicine, *RADIONUCLIDE imaging
Abstract

Molecular imaging is an important part of modern medicine which enables the non-invasive identification and characterization of diseases. With the advancement of radiochemistry and scanner technology, nuclear medicine is providing insight into efficient treatment options for individual patients. Titanium-45 (45Ti) is a lesser-explored radionuclide that is garnering increasing interest for the development of positron emission tomography (PET) radiopharmaceuticals. This review discusses aspects of this radionuclide including production, purification, radiochemistry development, and molecular imaging studies. [ABSTRACT FROM AUTHOR]

Published
2024
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48. [89Zr]-CD8 ImmunoPET imaging of glioblastoma multiforme response to combination oncolytic viral and checkpoint inhibitor immunotherapy reveals CD8 infiltration differential changes in preclinical models.

Author

Gallegos, Carlos A., Yun Lu, Clements, Jennifer C., Song, Patrick N., Lynch, Shannon E., Mascioni, Alessandro, Fang Jia, Hartman, Yolanda E., Massicano, Adriana V. F., Houson, Hailey A., Lapi, Suzanne E., Warram, Jason M., Markert, James M., and Sorace, Anna G.

Published
2024
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