Document text
Principal Investigator: Sheung Chee Thomas Ng
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2024
Award: $249,861
Funding agency: National Institute of Biomedical Imaging and Bioengineering
Immune-mediated positron emission tomography (immunoPET) is an emerging imaging technique that enables
non-invasive in vivo pathology assessment, analogous to what is commonly used in immunohistology. This is
enabled by imaging of radiolabeled antibodies or antibody fragments. However, current immunoPET
approaches, including pre-targeted strategies, suffer from relatively poor signal-to-background ratio, in part
because of the suboptimal pharmacokinetics of the imaging probes used. Moreover, widespread clinical
translation of current immunoPET technologies is hampered by the complexity of manufacturing individual
probes, supply chain constraints, and the complex workflow requiring patients to present to the hospital
multiple times in strict coordination for any individual immunoPET study. In this Trailblazer proposal, we posit
that lipid nanoparticle (LNP) technology can be harnessed for immunoPET to address several of the outlined
concerns. Extensive advances in LNP-mRNA now enable patients to be transient in vivo bioreactors for
therapeutic protein production, including antibodies and antibody fragments, offering an opportunity to improve
the kinetics of a protein-based imaging agent. Furthermore, LNP can be delivered via several routes that
potentially enable administration at a local pharmacy or even by self-administration. The purpose of this
Trailblazer proposal is to establish LNP-immunoPET as a viable platform for clinical molecular imaging. We will
assess the ability of LNP-mRNA to synthesize imageable antibody-based probes through radiohapten
interactions. Furthermore, we will assess the relationship of LNP administration route on the viability of the
LNP-immunoPET approach. If successful, LNP-immunoPET will offer a revolutionary strategy that will advance
the capability of immunoPET and extend the reach of molecular imaging and therapeutics for our patient
population.
Terms: <Acute Radiation Syndrome><Address><Adoption><Affect><Antibodies><Antibody Fragments><Benchmarking><Best Practice Analysis><Bi-specific antibodies><Bifunctional Antibodies><Binding><Bioreactors><Bispecific Antibodies><Body Tissues><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Cancers><Cell Communication and Signaling><Cell Signaling><Chemicals><Clinical><Complex><Development><Disease><Disorder><Drug Kinetics><Equity><Exhibits><FDA approved><FOLH><FOLH1><FOLH1 gene><Folate Hydrolase 1><GCP2><Glutamate Carboxypeptidase II><Goals><Half-Life><Health Care Systems><Healthcare Systems><Hospitals><Human><Image><Imaging Procedures><Imaging Technics><Imaging Techniques><Immune><Immunes><Immuno-PET><ImmunoPET><Immunoglobulin Fragments><Immunohistochemistry><Immunohistochemistry Cell/Tissue><Immunohistochemistry Staining Method><Individual><Infection><Inflammation><Injectable><Intracellular Communication and Signaling><Intravenous><Investigation><Kinetics><Label><Malignant Neoplasms><Malignant Tumor><Mediating><Messenger RNA><Mice><Mice Mammals><Mind><Modeling><Modern Man><Molecular Interaction><Murine><Mus><N-Acetylated Alpha-Linked Acidic Dipeptidase 1><NAALAD1><NAALADase I><PET><PET Scan><PET imaging><PETSCAN><PETT><PSM><PSMA><Pathology><Pathway interactions><Patients><Pharmacies><Pharmacokinetics><Pharmacology><Pharmacy facility><Population><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Production><Prostate-Specific Membrane Antigen><Proteins><Rad.-PET><Radiation Toxicity><Radioactive Isotopes><Radioimmunoconjugate><Radioisotopes><Radiolabeled><Radiolabeled Antibodies><Radionuclides><Radiotoxicity><Research Resources><Resources><Route><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><Self Administered><Self Administration><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><Signal Transduction><Signal Transduction Systems><Signaling><Socioeconomically disadvantaged><Staging><System><Techniques><Technology><Therapeutic><Time><Tissues><Tracer><Translations><Validation><benchmark><biological signal transduction><bsAb><chelation><clinical imaging><clinical translation><clinically translatable><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><developmental><facilities for imaging><imaging><imaging agent><imaging capabilities><imaging center><imaging facilities><imaging probe><imaging-related facilities><immune-PET><improved><in vivo><intravenous administration><intravenous injection><lipid based nanoparticle><lipid nanoparticle><mRNA><mRNA Expression><malignancy><manufacture><microbioreactor><molecular imaging><molecule imaging><mouse model><murine model><native protein drug><neoplasm/cancer><non-invasive imaging><noninvasive imaging><novel><optic imaging><optical imaging><pathway><patient population><pharmaceutical protein><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><primary care setting><prostate cancer model><prostate tumor model><protein drug agent><protein-based drug><radiation poisoning><radiolabel><radiolabeling><radiolabels><radiologically labeled><radiotracer><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><small molecule><socio-economic disadvantage><socio-economically disadvantaged><socio-economically underprivileged><socioeconomic disadvantage><socioeconomically underprivileged><subcutaneous><subdermal><supply chain><targeted imaging><therapeutic protein><translation><translational impact><tumor><uptake><validations><virtual monitoring>