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Immuno-PET in Non-Hodgkin lymphoma: A promising diagnostic advancement

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of blood cancers that affect the lymphatic system, particularly the lymphocytes (white blood cells), which are vital for immune function. Diagnosing and treating NHL can be difficult, because of the many different subtypes of NHL. The severity of the disease must be correctly diagnosed. The ability of traditional diagnostic techniques, like biopsies and imaging, to provide comprehensive information about the disease is limited. However, a cutting-edge technique called immuno-PET (Positron Emission Tomography) looks promising in the diagnosis and management of NHL [1,2]. In this blog, we will delve into the world of immuno-PET and its role in revolutionizing the management of NHL.


Non-Hodgkin lymphoma overview


Immuno-PET in Non-Hodgkin lymphoma

Before we dive into immuno-PET, let's briefly understand what NHL is. NHL refers to a group of lymphatic system cancers that primarily affect lymphocytes. These lymphomas are classified into various subtypes based on their cellular origin, behavior, and molecular characteristics, making NHL a complex and diverse group of diseases. The lymphatic tissue of organs like the stomach, intestines, or skin is where NHL typically originates. NHL can occasionally affect blood as well as bone marrow. In the body, lymphoma cells can form in one or several locations [1,2].


NHL is more common in developing countries and most frequently affects children under the age of 9 years. NHLs are considerably more aggressive than Hodgkin lymphoma; with intense chemotherapy, cure rates typically ranging from 70% to 90% depending on the subtype and the stage [1].


For directing decisions regarding treatment, an accurate diagnosis and staging are essential. Biopsy, blood testing, and traditional imaging techniques like CT scans and MRI have historically been preferred methods for diagnosing NHL. Even though these techniques have their advantages, they might not always give the whole story, which could result in treatment delays and substandard outcomes for patients [1].


Immuno-PET: The basics


PET is an imaging technique that depicts the body's metabolic activity using radioactive tracers. Immuno-PET is a method of whole-body molecular imaging that combines the high sensitivity, resolution, and quantitative capabilities of PET imaging with the unique binding properties of monoclonal antibodies. These monoclonal antibodies are designed to specifically bind to proteins or antigens found on the surface of the cancer cells. It has the potential to completely change how NHL is diagnosed, staged, and treated [1].


The current gold standard for staging and monitoring NHL is PET imaging with 18F-fluorodeoxyglucose (FDG). A radioactive tracer called FDG is absorbed by cells with high metabolic activity, including cancer cells. FDG can, however, be absorbed by various inflammatory cells and tissues and is not just specific for lymphoma. It might be challenging to determine the effectiveness of treatment because this can result in false positive and negative results [1].


Radionuclide imaging, specifically with PET (immuno-PET), offers a new opportunity to precisely evaluate the presence of tumor biomarkers in vivo. The presence of target antigens on tumor lesions has been verified by several preclinical studies using immuno-PET [2,3].


How does immuno-PET work?


Immuno-PET targets particular proteins in cancer cells using radiolabeled antibodies. Once the antibody is attached to the cancer cell, the radioactive tracer is internalized by the cell. After that, the tracer releases positrons which are detected by the PET scanner. This generates an image of the body that indicates the location of the cancer cells.


The most frequently used radiolabeled antibody for immuno-PET of NHL is [89Zr] rituximab, which targets the CD20 protein on B-cell lymphoma cells. Additionally, even though 89Zr has a larger effective dose than other traditional PET radionuclides (such as 18F), it is consistent with the amount of time required for a monoclonal antibody to acquire the ideal tumor-to-background ratio [3].


Furthermore, CD30 targeting is receiving a lot of interest. In clinical trials, CD30 is being tested in conjunction with chemotherapy and other monoclonal antibodies, such as the anti-PD-L1 pembrolizumab. It is an ideal target antigen for antibody-mediated drug delivery because it is overexpressed in lymphoma cells but not in healthy tissues and is easily internalized upon binding with brentuximab vedotin. Other radiolabeled antibodies are being developed to target additional proteins in NHL cells, including CD19, CD30, and CXCR4 [3].


Challenges and future directions


Immuno-PET is a promising new technique, but it is still in its infancy. Some challenges and limitations need to be addressed before they can be widely adopted in the clinic.

  • One challenge is the development of novel immuno-PET tracers with high affinity and specificity for lymphoma cells.

  • Another challenge is the development of standardized imaging and quantification techniques.

  • Immuno-PET's accessibility and cost may further restrict its utilization for some patients. Immuno-PET is more expensive than FDG-PET, although it is not yet generally accessible in all healthcare settings.

Future applications of immuno-PET in lymphomas, nevertheless, could be made possible through ongoing research. This is vital in overcoming the main limitation of the traditional [18F]FDG PET/CT in terms of the detection of metabolically inert lymphoma cells [3,4].


End of the line


Immuno-PET represents a groundbreaking advancement in the field of NHL diagnosis and treatment. Its capacity to deliver extremely accurate and sensitive imaging of malignant tissue has the potential to completely change how we diagnose and treat NHL. This imaging technique may offer a promising route for enhancing the efficacy of immunotherapy while lowering toxicity and expenses.


References


1. Guja, K.E. et al. 'Overview and Recent Advances in 18F-FDG PET/CT for Evaluation of Pediatric Lymphoma'. Seminars in Nuclear Medicine. (2023) 53(3), 400–412. DOI: 10.1053/j.semnuclmed.2022.10.001.

2. Lee, K.-H. et al. 'Immuno-PET Imaging and Radioimmunotherapy of Lymphomas'. Molecular Pharmaceutics. (2022). DOI: 10.1021/acs.molpharmaceut.2c00563.

3. Triumbari, E.K.A. et al. 'Clinical Applications of Immuno-PET in Lymphoma: A Systematic Review'. Cancers (Basel). (2022) 14(14), 3488. DOI: 10.3390/cancers14143488.

4. Manafi-Farid, R. et al. 'ImmunoPET: Antibody-Based PET Imaging in Solid Tumors'. Frontiers in Medicine. (2022) 9.

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