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Principal Investigator: Jan Grimm
Organization: SLOAN-KETTERING INST CAN RESEARCH
Fiscal Year: 2024
Award: $627,848
Funding agency: National Institute of Biomedical Imaging and Bioengineering
SUMMARY: The problem: In molecular medicine multiple parameters are combined for a more inclusive
evaluation towards personalized medicine. A thorough characterization of a patient’s tumor upfront provides
better outcomes, i.e., better insight affords higher survival rates. In contrast and almost anachronistically, PET
imaging (the most sensitive and quantitative imaging method) is “monochromatic” as it can only assess one
parameter at the time, lacking depth of information. Suitable imaging tools that allow visualization of more than
one target in patients are needed, akin an in vivo cytometry. Optical imaging utilizes multiple parts of the
spectrum to visualize several targets simultaneously, but this is not feasible for whole-body clinical imaging due
to the limited penetration of light. Single-photon emission computed tomography (SPECT) can distinguish
several isotopes based on the energy of their emissions, but spectra often overlap and the required collimation
significantly decreases sensitivity. Different tracers could be imaged sequentially with PET but multiple scans
increase the dose exposure from the required CT scans. It also requires sufficient decay of one tracer over time
to be able to image the remaining one, decreasing convenience for patients. For three or four different isotopes
this requires an even more complex coordination. As a solution, we propose the new modality of multicolor PET
(mPET), which allows for simultaneous PET acquisitions of up to four different radiotracers at the same time.
This new imaging paradigm utilizes one standard (pure) positron emitter together with positron-gamma emitters
that produce triple (positron-gamma) coincidences, where a prompt gamma emission immediately follows the
positron and identifies the isotope. We already imaged two isotopes in a standard PET scanner with the aid of
the additional gamma signal but without energy discrimination. Here, we utilize the energy of the gamma signal
as “barcode identifier” for the corresponding isotope while the spatial information is carried with the 511 keV
annihilation photons. The prompt gamma requires detection without spatial decoding, which is achieved by an
add-on gamma detector with sufficient energy discrimination and temporal resolution that is synchronized with
the PET scanner. We established this system already and imaged three isotopes together. Here, we will in Aim
1 optimize the mPET set-up and then employ mPET to address important clinical/biological problems: In Aim 2,
we will dissect the tumor microenvironment, interrogating signatures important for prognosis. In Aim 3, we will
use mPET to interrogate important players in checkpoint inhibition therapy (CD4+ / CD8+ / PD-L1 /
macrophages) simultaneously over time to predict response and will explore cellular therapies by following the
injected cells to their target. The overall impact of this study will be significant, as mPET represents a true
paradigm shift, allowing imaging of several radiotracers simultaneously. We demonstrate the power of this novel
approach with clinically relevant approaches. More tracers asses a tumor better than one tracer alone, will
provide a deeper insight into relevant tumor signatures, resulting in improved patient outcome.
Terms: <18-FDG><18F- FDG><18FDG><2 Fluoro 2 deoxy D glucose><2-Fluoro-2-deoxyglucose><ASCO><Address><Advanced Cancer><Advanced Malignant Neoplasm><Affect><American Society of Clinical Oncology><Animals><Antibodies><Assay><B7-H1><B7H1><Bar Codes><Bioassay><Biological><Biological Assay><Biopsy><CAR T cells><CAR modified T cells><CAR-T><CAR-Ts><CAT scan><CD274><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><CT X Ray><CT Xray><CT imaging><CT scan><Cancer Biology><Cancer Patient><Cancer Treatment><Cancers><Cell Body><Cell Communication and Signaling><Cell Signaling><Cell Therapy><Cells><Clinical><Cognitive Discrimination><Collimation><Collimator><Color><Complex><Computed Tomography><Cytometry><Detection><Discrimination><Dose><Evaluation><Event><FDA approved><Fibroblasts><Gamma Radiation><Gamma Rays><Genetic Alteration><Genetic Change><Genetic defect><Image><Imaging Device><Imaging Instrument><Imaging Tool><Immune><Immune mediated therapy><Immune system><Immunes><Immunologically Directed Therapy><Immunotherapy><Individual><Intracellular Communication and Signaling><Isotopes><LYT3><Lead><Light><Literature><Location><MSKCC><Macrophage><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Measures><Memorial Sloan-Kettering Cancer Center><Methods><Modality><Modernization><Molecular Fingerprinting><Molecular Medicine><Molecular Profiling><Monitor><Mutation><Mφ><Oncology><Oncology Cancer><Outcome><PD-L1><PDL-1><PDL1><PET><PET Scan><PET imaging><PETSCAN><PETT><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pb element><Penetration><Photons><Photoradiation><Positron><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Prognosis><Programmed Cell Death 1 Ligand 1><Programmed Death Ligand 1><Rad.-PET><Radiolabeled><Resolution><Rest><Role><SPECT><SPECT imaging><Scanning><Signal Transduction><Signal Transduction Systems><Signaling><Single-Photon Emission-Computed Radionuclide Tomography><Survival Rate><System><T cells for CAR><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Testing><Therapeutic><Time><Tomodensitometry><Tracer><Tumor Antigens><Tumor Cell><Tumor Volume><Tumor-Associated Antigen><Visualization><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><actionable mutation><actionable variants><anti-cancer therapy><anti-tumor immune therapy><anti-tumor immunotherapy><barcode><biologic><biological signal transduction><cancer antigens><cancer imaging><cancer microenvironment><cancer progression><cancer therapy><cancer-directed therapy><catscan><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><check point inhibition><checkpoint inhibition><chimeric antigen T cell receptor><chimeric antigen receptor (CAR) T cells><chimeric antigen receptor T cells><chimeric antigen receptor fusion protein T-cells><chimeric antigen receptor modified T cells><clinical care><clinical imaging><clinical relevance><clinically relevant><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><cost><detector><fluorodeoxyglucose><frontier><genome mutation><genome profiling><genomic profiling><heavy metal Pb><heavy metal lead><image-based method><imaging><imaging method><imaging modality><immune check point inhibition><immune checkpoint inhibition><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><improved><in vivo><insight><malignancy><molecular profile><molecular signature><nano medicinal><nano medicine><nanomedicinal><nanomedicine><neoplasm immunotherapy><neoplasm progression><neoplasm/cancer><neoplastic cell><neoplastic progression><new approaches><next generation><non-contrast CT><noncontrast CT><noncontrast computed tomography><novel><novel approaches><novel strategies><novel strategy><oncologic imaging><oncology imaging><optic imaging><optical imaging><patient oriented outcomes><patient stratification><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><predict responsiveness><predicting response><programmed cell death ligand 1><programmed cell death protein ligand 1><protein death-ligand 1><public health relevance><quantitative imaging><radiolabel><radiolabeling><radiolabels><radiologically labeled><radiotracer><reconstruction><resolutions><response><response to therapy><response to treatment><single photon 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