The Unique Pharmacometrics of Small Molecule Therapeutic Drug Tracer Imaging for Clinical Oncology

Dunphy, Mark; Pillarsetty, Nagavarakishore

doi:10.3390/cancers12092712

Cited by 7 publications

(4 citation statements)

References 94 publications

(132 reference statements)

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“…Small molecule-based tumor-targeted probes, such as peptide-or affibody-targeted probes, have fast renal clearance and enable high tumor-to-background imaging within a few hours postadministration. [40][41][42] This is critical for same-day administration of the tumor-targeted probes followed by surgical procedures, which can reduce healthcare costs and avoid hospital infections by minimizing hospital stays. Therefore, we evaluated the limit of detection for two small moleculebased tumor-targeted probes: (1) IR680-integrin and (2) IR800-EGF.…”

Section: Limit Of Detection For Small Molecule Tumor Targeted Probesmentioning

confidence: 99%

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery

et al. 2023

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Significance: Fluorescently guided minimally invasive surgery is improving patient outcomes and disease-free survival, but biomarker variability hinders complete tumor resection with single molecular probes. To overcome this, we developed a bioinspired endoscopic system that images multiple tumor-targeted probes, quantifies volumetric ratios in cancer models, and detects tumors in ex vivo samples.Aim: We present a new rigid endoscopic imaging system (EIS) that can capture color images while simultaneously resolving two near-infrared (NIR) probes.Approach: Our optimized EIS integrates a hexa-chromatic image sensor, a rigid endoscope optimized for NIR-color imaging, and a custom illumination fiber bundle.Results: Our optimized EIS achieves a 60% improvement in NIR spatial resolution when compared to a leading FDA-approved endoscope. Ratio-metric imaging of two tumor-targeted probes is demonstrated in vials and animal models of breast cancer. Clinical data gathered from fluorescently tagged lung cancer samples on the operating room's back table demonstrate a high tumor-to-background ratio and consistency with the vial experiments. Conclusions:We investigate key engineering breakthroughs for the single-chip endoscopic system, which can capture and distinguish numerous tumor-targeting fluorophores. As the molecular imaging field shifts toward a multi-tumor targeted probe methodology, our imaging instrument can aid in assessing these concepts during surgical procedures.

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Section: Limit Of Detection For Small Molecule Tumor Targeted Probesmentioning

confidence: 99%

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery

et al. 2023

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“…Properties. The properties of PSMA-targeting tracers differ on several key features, which results in different strategies for targeting PSMA [26]. For example, some tracers are small-molecule inhibitors while others are monoclonal antibodies [27].…”

Section: Psma-targeting Pet Tracermentioning

confidence: 99%

Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors

et al. 2022

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Introduction. Positron emission tomography (PET) imaging with prostate-specific membrane antigen- (PSMA-) binding tracers has been found incidentally to demonstrate uptake in CNS tumors. Following the encouraging findings of several such case reports, there is a growing interest in the potential application of PSMA-targeted PET imaging for diagnostics, theranostics, and monitoring of CNS tumors. This is a systematic literature review on PSMA-binding tracers in CNS tumors. Methods. A PubMed search was conducted, including preclinical and clinical reports. One hundred and twelve records were identified, and after screening, 56 were included in the final report. Results. Tissue studies demonstrated PSMA expression in tumor vascular endothelial cells, without expression in normal brain tissue, though the extent and intensity of staining varied by anti-PSMA antibody and methodology. Most included studies reported on gliomas, which showed strong PSMA ligand uptake and more favorable tumor to background ratios than other PET tracers. There are also case reports demonstrating PSMA ligand uptake in prostate cancer brain metastases, nonprostate cancer brain metastases, and meningiomas. We also review the properties of the various PSMA-binding radiotracers available. Therapeutic and theranostic applications of PSMA-binding tracers have been studied, including labeled alpha- and beta-ray emitting isotopes, as well as PSMA targeting in directing MRI-guided focused ultrasound. Conclusions. There is a potential application for PSMA-targeted PET in neuro-oncology as a combination of diagnostic and therapeutic use, as a theranostic modality for managing CNS tumors. Further research is needed regarding the mechanism(s) of PSMA expression in CNS tumors and its differential performance by tumor type.

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“…Moreover, because some of these molecules are also able to diffuse across the blood brain barrier (BBB), they can be used for targeting cancers involving the central nervous system. [51] Many small molecules have been designed to modulate signaling pathways by activation or inhibition of proteins involved in cancer proliferation, migration and survival. [52] Over the years, advances in radiochemistry have made labeling of these compounds into a favored strategy, yielding successful diagnostic and therapeutic radiotracers.…”

Section: Personalized Therapymentioning

confidence: 99%

Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

et al. 2021

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Nuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are based on γ-emissions of specific energies. The therapeutic technologies are based on β À -particle-, α-particle-, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease's progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost-efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.

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The Unique Pharmacometrics of Small Molecule Therapeutic Drug Tracer Imaging for Clinical Oncology

Cited by 7 publications

References 94 publications

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery

Bioinspired color-near infrared endoscopic imaging system for molecular guided cancer surgery

Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors

Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

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