journal article·2024-09-27Open access

Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY)

Michele Moreau, Debarghya China, Gnagna Sy, Kai Ding, Wilfred Ngwa

Journal of Functional Biomaterials· Volume 15· Issue 10

Abstract

Smart radiotherapy biomaterials (SRBs) include seed and liquid biomaterials designed to be employed as fiducial markers during radiotherapy while also delivering therapeutic drug payloads to enhance treatment outcomes. In this study, we investigate a novel Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY) biomaterial, which can be loaded with immunoadjuvants (anti-CD40 monoclonal antibody or Caflanone (FBL-03G)) at the point of care. The CLARITY biomaterial was investigated in an animal model of pancreatic cancer using C57BL6 mice. Mice were imaged before and at different points of time post-treatment to evaluate the potential of CLARITY biomaterial to provide imaging contrast similar to fiducials. This study also used cadavers to assess CLARITY’s potential to provide imaging contrast in humans. Results showed imaging contrast from computed tomography (CT) and magnetic resonance imaging (MRI) modalities for up to 30 days post-treatment, demonstrating potential for use as fiducials. A significant increase in survival (***, p = 0.0006) was observed for mice treated with CLARITY biomaterial loaded with immunoadjuvant for up to 10 weeks post-treatment compared to those without treatment. These initial results demonstrate the potential of CLARITY biomaterial to serve as a smart multifunctional radiotherapy biomaterial and provide the impetus for further development and optimization as a point-of-care technology for combination radiotherapy and immunotherapy.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Nanoplatforms for cancer theranostics · Advanced Radiotherapy Techniques · Medical Imaging Techniques and Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA

Funding

National Cancer Institute/NIH/DHHS

References (44)

Show source-provided references
1. CT-Based Delineation of Organs at Risk in the Head and Neck Region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG Consensus Guidelines10.1016/j.radonc.2015.07.041 ↗
2. Guidance Document on Delivery, Treatment Planning, and Clinical Implementation of IMRT: Report of the IMRT Subcommittee of the AAPM Radiation Therapy Committee10.1118/1.1591194 ↗
3. Intensity Modulation to Improve Dose Uniformity with Tangential Breast Radiotherapy: Initial Clinical Experience10.1016/S0360-3016(00)01396-1 ↗
4. Overview of Image-Guided Radiation Therapy10.1016/j.meddos.2005.12.004 ↗
5. Young, M.R., and Yu, J.B. (2016). Intensity Modulated Radiotherapy and Image Guidance. Prostate Cancer, Elsevier.10.1016/B978-0-12-800077-9.00045-1 ↗
6. Impact of Fiducial Marker Placement Before Stereotactic Body Radiation Therapy on Clinical Outcomes in Patients With Pancreatic Cancer10.1016/j.adro.2020.11.006 ↗
7. Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy10.3390/curroncol30050382 ↗
8. Transperineal Implantation of Gold Fiducial Markers (Gold Seeds) for Prostate Image-guided Radiation Therapy: A Feasible Technique Associated with a Low Risk of Complications10.1002/jmrs.122 ↗
9. Feasibility of a Novel Liquid Fiducial Marker for Use in Image Guided Radiotherapy of Oesophageal Cancer10.1259/bjr.20180236 ↗
10. Clinical and Dosimetric Comparison Between Non-Image Guided Radiation Therapy and Fiducial-Based Image Guided Radiation Therapy With or Without Reduced Margin in Intensity Modulated Radiation Therapy for Prostate Cancer10.1016/j.adro.2024.101612 ↗
11. Camus, M., Karsenti, D., Levy, J., Moreno, M., Coron, E., Esch, A., Williet, N., Wangermez, M., Koch, S., and Valats, J.C. (Gastrointest. Endosc., 2024). Success Rate of Fiducial Markers Placement for Treatment of Esophageal or Rectal Cancers, a Prospective Multicenter Study (FIDECHO Study), Gastrointest. Endosc., online ahead of print.10.1016/j.gie.2024.08.014 ↗
12. Sarma, G., Kashya, H., Medhi, P.P., Kalita, R., and Lahkar, D. (2024). Unravelling the Landscape of Image-Guided Radiotherapy: A Comprehensive Overview. Palliat. Med. Pract.10.5603/pmp.100218 ↗
13. The First Clinical Implementation of Real-Time 6 Degree-of-Freedom Image-Guided Radiotherapy for Liver SABR Patients10.1016/j.radonc.2023.110031 ↗
14. Cone-Beam Computed Tomography-Guided Online Adaptive Radiotherapy: Promising Results for Bladder Cancer Case
15. Moreau, M., Acter, S., Ngema, L.M., Bih, N., Sy, G., Keno, L.S., Chow, K.F., Sajo, E., Nebangwa, O., and Walker, J. (2023). Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (ISRB). Pharmaceutics, 15.10.3390/pharmaceutics15122778 ↗
16. BioXmark® Liquid Fiducials to Enable Radiotherapy Tumor Boosting in Rectal Cancer, a Feasibility Trial
17. Moreau, M., Richards, G., Yasmin-Karim, S., Narang, A., Deville, C., and Ngwa, W. (2022). A Liquid Immunogenic Fiducial Eluter for Image-Guided Radiotherapy. Front. Oncol., 12.10.3389/fonc.2022.1020088 ↗
18. Moreau, M., Keno, L.S., China, D., Mao, S., Acter, S., Sy, G., Hooshangnejad, H., Chow, K.F., Sajo, E., and Walker, J. (2024). Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment. Cancers, 16.10.3390/cancers16061212 ↗
19. Smart Radiation Therapy Biomaterials10.1016/j.ijrobp.2016.10.034 ↗
20. Nanogels: An Overview of Properties, Biomedical Applications and Obstacles to Clinical Translation10.1016/j.jconrel.2015.11.009 ↗
21. Tripathy, S., Verma, D.K., Gupta, A.K., Srivastav, P.P., Patel, A.R., Chávez González, M.L., Utama, G.L., and Aguilar, C.N. (2023). Nanoencapsulation of Biofunctional Components as a Burgeoning Nanotechnology-Based Approach for Functional Food Development: A Review. Biocatal. Agric. Biotechnol., 53.10.1016/j.bcab.2023.102890 ↗
22. Multifunctional PVCL Nanogels with Redox-Responsiveness Enable Enhanced MR Imaging and Ultrasound-Promoted Tumor Chemotherapy10.7150/thno.43402 ↗
23. Gadolinium Oxide Nanoplates with High Longitudinal Relaxivity for Magnetic Resonance Imaging10.1039/C4NR03505D ↗
24. Gadolinium-Loaded Poly(N -Vinylcaprolactam) Nanogels: Synthesis, Characterization, and Application for Enhanced Tumor MR Imaging10.1021/acsami.6b14219 ↗
25. Hollow MnO2 as a Tumor-Microenvironment-Responsive Biodegradable Nano-Platform for Combination Therapy Favoring Antitumor Immune Responses10.1038/s41467-017-01050-0 ↗
26. Relaxivity and Toxicological Properties of Manganese Oxide Nanoparticles for MRI Applications10.1039/C6RA04421B ↗
27. Martinez de la Torre, C., Grossman, J.H., Bobko, A.A., and Bennewitz, M.F. (2020). Tuning the Size and Composition of Manganese Oxide Nanoparticles through Varying Temperature Ramp and Aging Time. PLoS ONE, 15.10.1371/journal.pone.0239034 ↗
28. Nie, D., Zhu, Y., Guo, T., Yue, M., and Lin, M. (2022). Research Advance in Manganese Nanoparticles in Cancer Diagnosis and Therapy. Front. Mater., 9.10.3389/fmats.2022.857385 ↗
29. Theranostic 2D Ultrathin MnO2 Nanosheets with Fast Responsibility to Endogenous Tumor Microenvironment and Exogenous NIR Irradiation10.1016/j.biomaterials.2017.11.015 ↗
30. Manganese Oxide Nano-Platforms in Cancer Therapy: Recent Advances on the Development of Synergistic Strategies Targeting the Tumor Microenvironment10.1016/j.apmt.2022.101628 ↗
31. Manganese Oxide Nanomaterials: Synthesis, Properties, and Theranostic Applications10.1002/adma.201905823 ↗
32. Cancer Statistics, 202410.3322/caac.21820 ↗
33. Cancer Statistics 2024: All Hands on Deck10.3322/caac.21824 ↗
34. Early Detection of Pancreatic Cancer—A Defined Future Using Lessons From Other Cancers10.1097/MPA.0000000000000701 ↗
35. Pancreatic Ductal Adenocarcinoma Epidemiology and Risk Assessment: Could We Prevent? Possibility for an Early Diagnosis10.4103/eus.eus_60_17 ↗
36. Time to Progression of Pancreatic Ductal Adenocarcinoma from Low-to-High Tumour Stages10.1136/gutjnl-2014-308653 ↗
37. He, R., Jiang, W., Wang, C., Li, X., and Zhou, W. (2024). Global Burden of Pancreatic Cancer Attributable to Metabolic Risks from 1990 to 2019, with Projections of Mortality to 2030. BMC Public Health, 24.10.1186/s12889-024-17875-6 ↗
38. Why Do Black Americans Have a Higher Risk of Pancreatic Cancer than White Americans?10.1097/00001648-200301000-00013 ↗
39. Transperineal versus Transrectal Prostate Fiducial Insertion in Radiation Treatment of Prostate Cancer: A Systematic Review and Meta-Analysis10.14366/usg.23229 ↗
40. Displacements of Fiducial Markers in Patients with Prostate Cancer Treated with Image Guided Radiotherapy: A Single-Institution Descriptive Study10.1016/j.rpor.2014.08.002 ↗
41. Liu, X., Kifle, M.T., Xie, H., Xu, L., Luo, M., Li, Y., Huang, Z., Gong, Y., Wu, Y., and Xie, C. (2022). Biomineralized Manganese Oxide Nanoparticles Synergistically Relieve Tumor Hypoxia and Activate Immune Response with Radiotherapy in Non-Small Cell Lung Cancer. Nanomaterials, 12.10.3390/nano12183138 ↗
42. Huang, Y., Ruan, Y., Ma, Y., Chen, D., Zhang, T., Fan, S., Lin, W., Huang, Y., Lu, H., and Xu, J.-F. (2023). Immunomodulatory Activity of Manganese Dioxide Nanoparticles: Promising for Novel Vaccines and Immunotherapeutics. Front. Immunol., 14.10.3389/fimmu.2023.1128840 ↗
43. Synthesis and Characterization of Lyophilized Chitosan-Based Hydrogels Cross-Linked with Benzaldehyde for Controlled Drug Release10.1155/2020/8747639 ↗
44. Synthesis and Evaluation of Alginate-Based Nanogels as Sustained Drug Carriers for Caffeine10.1021/acsomega.3c02699 ↗