Positron Emission Tomography of CD47/SIRPα Axis and Image-Informed Therapeutic Design

bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-29

CD47/SIRPα immune axis is of substantial clinical interest for innate cancer immunotherapy. Development on this axis has largely focused on monoclonal antibody agents and combination therapy strategies. Clinical use is challenging due to dose limiting side effects and severe anemia. Better understanding of the whole-body dynamics of CD47/SIRPα can be used to improve the developmental and therapeutic strategies targeting this axis. Herein, we developed anti-CD47 and anti-SIRPα radiotracers with good yields and stability. CD47/SIRPα biodistribution showed consistent whole-body results in healthy and colorectal cancer (CT26) allograft mice, demonstrating significant uptake in normal organs liver and spleen in addition to tumor accumulation of these agents. Enhancing immunogenicity via low-dose radiotherapy had no impact on over-all biodistribution but caused small, significant changes for anti-SIRPα tumor uptake. Antibody PEGylation of the anti-SIRPα tracer was further able to modify the whole-body distribution and reduce splenic uptake. These findings suggest that SIRPα targeted agents may benefit from co-therapies and drug delivery systems to optimize tumor uptake. Our work highlights the importance of in vivo molecular imaging in addition to in vitro and ex vivo assays when evaluating therapeutic designs.

FOLR1-targeted Actinium-225-based Alpha-particle Therapy Eliminates Ovarian Cancer

bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-27

Abstract Despite the advancement in therapies, ovarian cancer treatment is challenging due to poor prognosis and high relapse associated with acquired resistance. Targeting overexpression of FOLR1 in ovarian cancers has proven to be an attractive strategy. The recent FDA approval of FOLR1 targeted antibody drug conjugate has shown promising results albeit resistance with repeated use appears inevitable. Emerging targeted alpha-particle therapies, particularly Actinium-225 ( 225 Ac), for treating refractory cancers have opened avenues for improved therapeutic options. The success of alpha-particle therapy relies on tumor specific delivery of the alpha emitters. Herein we describe the first example of FOLR1-targeted 225 Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal PET imaging demonstrated high tumor-specific uptake of αFOLR1 in SKOV3 xenografts. FOLR1-targeted 225 Ac demonstrated high therapeutic efficacy achieving marked tumor regression, 80% survival and 40% complete response. The therapy resulted in tumor specific double stranded DNA damage, and no obvious toxicity was observed in normal tissues. Estimated human dosimetry showed high absorbed dose for tumor and minimal absorbed dose for healthy tissues establishing its safety. In totality, FOLR1-targeted 225 Ac alpha-particle therapy is an efficacious and safe treatment with high feasibility for clinical translation to fight against ovarian cancer.

Image-guided targeting of mitochondrial metabolism sensitizes pediatric malignant rhabdoid tumors to low-dose radiotherapy

Science Advances · 2025-05-23 · 4 citations

Tumor hypoxia leads to radioresistance and markedly worse clinical outcomes for pediatric malignant rhabdoid tumors (MRTs). Our transcriptomics and bioenergetic profiling data reveal that mitochondrial oxidative phosphorylation is a metabolic vulnerability of MRT and can be exploited to overcome consumptive hypoxia by repurposing an FDA-approved antimalarial drug, atovaquone (AVO). We then establish the utility of oxygen-enhanced-multispectral optoacoustic tomography, a label-free, ionizing radiation-free imaging modality, to visualize and quantify spatiotemporal changes in tumor hypoxia in response to AVO. We show a potent but transient increase in tumor oxygenation upon AVO treatment that results in complete elimination of tumors in all tested mice when combined with 10-gray radiotherapy, a dose several times lower than the current clinic standard. Last, we use translational mathematical modeling for systematic evaluation of dosing regimens, administration timing, and therapeutic synergy in a virtual patient cohort. Together, our work establishes a framework for safe and pediatric patient-friendly image-guided metabolic radiosensitization of rhabdoid tumors.

Image-Guided Targeting of Mitochondrial Metabolism Sensitizes Pediatric Malignant Rhabdoid Tumors to Low Dose Radiotherapy

bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-10

Tumor hypoxia leads to radioresistance and markedly worse clinical outcomes for pediatric malignant rhabdoid tumors (MRT). Our transcriptomics and bioenergetic profiling data reveal that mitochondrial oxidative phosphorylation (OXPHOS) is a metabolic vulnerability of MRT and can be exploited to overcome consumptive hypoxia by repurposing an FDA-approved anti-malarial drug, Atovaquone (AVO). We then establish the utility of Oxygen-Enhanced-Multispectral Optoacoustic Tomography (OE-MSOT), a label-free, ionizing radiation-free imaging modality, to visualize and quantify spatiotemporal changes in tumor hypoxia in response to AVO. We show a potent but transient increase in tumor oxygenation upon AVO treatment which results in complete elimination of tumors in all tested mice when combined with 10 Gy radiotherapy, a dose several times lower than the current clinic standard. Finally, we use translational mathematical modeling for systematic evaluation of dosing regimens, administration timing, and therapeutic synergy in a virtual clinical patient population. Together, our work establishes a framework for safe and pediatric patient-friendly image-guided metabolic radiosensitization of rhabdoid tumors.

Tumor agnostic ultrasmall nanoprobes for fluorescence-guided surgical resection in peritoneal metastasis

European Journal of Nuclear Medicine and Molecular Imaging · 2024-10-24

Evaluations of a Cutaneous Wound Healing Model Using Oxygen Enhanced – Dynamic Contrast Enhanced Photoacoustic Imaging (OE-DCE PAI)

Molecular Imaging and Biology · 2024-11-12 · 4 citations

Prevalence of rapid calculus formers and its associated factors amongst patients visiting a dental hospital: a preliminary investigation

BMC Oral Health · 2024-08-16 · 1 citations

BACKGROUND: This study focuses on the determination and classification of patients as rapid or slowcalculusformersbasedontherateofcalculusformationafteroralprophylaxis. It also aims to determine the factors that positively impact the formation and deposition of calculus in patients and identify the factors that accelerate or decelerate the deposition of calculus. METHODS: The study was conducted in the Department of Periodontology, Dr Harvansh Singh Judge Institute of Dental Sciences and Hospital, Panjab University Chandigarh, India. We examined 51 patients after a month of the oral prophylaxis, recorded the amount of calculus present in the oral cavity, and then recorded a detailed history which was briefly divided into Age, Sex, Residence, Oral habits, and maintenance of oral hygiene. RESULTS: An evident and meaningful link was found between age and the rate at which dental calculus forms. The average age of individuals differed significantly between the rapid and slow calculus formers, which could be ascribed to the decline in manual dexterity as age increases, resulting in less effective oral hygiene habits, including toothbrushing. None of the other factors dietary and oral hygiene related could be identified distinctly, probably owing to the small sample of the study. The oral health status exhibited a significant difference between slow and rapid calculus formers. CONCLUSIONS: Within the limitations of the study, the data analyzed, identified age as a significant determinant that impact the rate of formation of calculus in patients and reported a significant difference in the oral health status of rapid and slow calculus formers.

Molecular imaging of innate immunity and immunotherapy

Advanced Drug Delivery Reviews · 2023-05-12 · 13 citations

Evaluations of radiotherapy in small animal models of pancreatic cancer with oxygen enhanced–dynamic contrast enhanced multispectral optoacoustic tomography (OE-DCE MSOT)

2023-01-26 · 6 citations

Tumor hypoxia causes resistance to radiotherapy. A non-invasive imaging method is needed to quantitatively measure tumor hypoxia to predict radiotherapy response before starting treatment. Furthermore, radiotherapy can damage blood vessels, which can reduce vascular perfusion and oxygen delivery. We have developed Oxygen Enhanced – Dynamic Contrast Enhanced Multispectral Optoacoustic Tomography (OE-DCE MSOT) that can evaluate hypoxia and vascular perfusion in a single scan session. OE MSOT measures oxygen saturation with medical grade air (%sO₂ ^airusing 21% O₂) breathing gas and 100% breathing gas (%sO₂ ^O2), and the “available oxygen capacity” (ΔsO2) that is the difference between %sO₂ ^air and %sO² ^air . DCE MSOT uses the normalized pharmacokinetics profile of an exogenous contrast agent in a tumor to calculate NKtrans and kep, which indicate the wash-in and wash-out vascular perfusion rates, respectively. We have shown that our DCE MSOT methodology avoids the problem of variable fluence within in vivo tissues. We applied OE-DCE MSOT to study the effect of radiotherapy on three tumor models that have different levels of vascular perfusion and hypoxia. Our results showed that %sO2 ^air , %sO₂ ^O2 , ΔsO₂ identified normoxic, mildly hypoxic, and hypoxic models, which was related to the high-to-low status of vascular perfusing as measured with NKtrans . A change in ΔsO₂ and NKtrans indicated early response to radiotherapy. These results demonstrate the advantages of OE-DCE MSOT for simultaneously evaluating tumor hypoxia and vascular perfusion before and soon after treatment.

Analysis of hematology quality control using six sigma metrics

Indian Journal of Pathology and Microbiology · 2023-11-09 · 5 citations

INTRODUCTION: Clinical laboratories serve a critical role in increasing the efficiency of patient care. Choosing the right test, getting trustworthy results and appropriate interpretation are of utmost importance in improving the patient's well-being. Quality management strategies should be applied in routine patient care because laboratory errors have a major impact on the quality of patient care. In sigma metrics, errors identified are quantified as percentage errors or defects per million (DPM). It aims at improving the quality control (QC) process by forming an appropriate strategy. AIM AND OBJECTIVES: To analyze the internal quality control (IQC) of hematology analytes using the sigma metrics method and to devise the frequency of IQC by the results of six sigma metric analysis. MATERIALS AND METHODS: This study was conducted in a tertiary care center of western India. Internal quality control (IQC) data sets of five analytes- Red Blood Cell count (RBC), Hemoglobin (Hb), Hematocrit (Hct), White blood cell count (WBC), and Platelet count (PLT) were analyzed retrospectively of six months using Beckman Coulter DXH 800 hematology analyzers. RESULTS: The observed sigma value was >6 for Hb, TLC, and PLT, indicating excellent results and requiring no modification in IQC. The Sigma value was between 3 and 4 for RBC and Hct suggested the need for improvement in quality control (QC) processes. No analytes showed a Sigma value of <3. CONCLUSION: Sigma metrics provide a quantitative framework that helps to assess analytic methodologies and can serve as an important self-assessment tool for quality assurance in the clinical laboratory.