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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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8. 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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20. 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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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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41. 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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45. [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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