Efficacy of 68Ga-Pentixafor PET/MR in Detecting Non-Hodgkin Lymphoma and Multiple Myeloma Lesions

The hematolymphatic system comprises blood, lymph nodes, extranodal lymphatic tissues, bone marrow, and the spleen. When malignant transformations occur within this system, they often infiltrate various tissues and organs throughout the body. Therefore, a comprehensive assessment of all tissues and organs is necessary to delineate the lesions' extent and conduct clinical staging to guide treatment. Lymphoma is the most prevalent malignancy of the hematologic system, with non-Hodgkin lymphoma (NHL) accounting for a significant incidence within this category, representing approximately 90% of lymphomas in our country. The clinical classification of NHL is complex, exhibiting considerable heterogeneity in biological behavior, immunophenotyping, and prognosis. The main subtypes include diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), T-cell lymphoma (TCL), marginal zone lymphomas (MZL), and mantle cell lymphoma (MCL). Multiple myeloma (MM) is a malignant disease characterized by the clonal proliferation of abnormal plasma cells and is the second most common hematologic malignancy following lymphoma. Common symptoms include organ dysfunction related to myeloma, encapsulated in the "CRAB" criteria-hypercalcemia, renal insufficiency, anemia, and bone disease-along with manifestations of organ damage due to amyloidosis. The prognosis is poor if patients do not receive timely and effective treatment.

Chemokine receptor 4 (CXCR4) is a member of the C-X-C motif (CXC) subfamily of chemokine receptors and is widely expressed in various types of organ tissue. It significantly regulates numerous physiological processes through interaction with CXC-chemokine ligand 12 (CXCL12). The CXCR4/CXCL12 biological axis is critical in the proliferation, invasion, and metastasis of NHL and MM and is considered a marker of poor prognosis. Recently, a new positron emission tomography (PET) tracer targeting CXCR4, 68Ga-Pentixafor, has been developed and is being increasingly utilized to diagnose hematological malignancies. The 68Ga-Pentixafor PET demonstrates notable advantages in identifying lymphoma, particularly indolent types, as well as in detecting early small lesions associated with MM. It shows greater sensitivity compared to 18F-fluorodeoxyglucose (FDG) imaging. This advancement not only enhances patient diagnosis and efficacy evaluation but also functions as a biological targeting molecule for individuals with poor prognostic outcomes, enabling these patients to access more intensive treatment options.

18F-fluorodeoxyglucose (FDG) is the most widely used tracer in nuclear medicine for tumor imaging, applicable to the initial staging and efficacy assessment of the vast majority of tumors. According to the 2021 guidelines from the Chinese Medical Association's Nuclear Medicine Branch and recommendations from the International Myeloma Working Group (IMWG), 18F-FDG positron emission tomography / computed tomography (PET/CT) imaging is recommended for the diagnostic and therapeutic management of all lymphoma and MM patients. However, it is important to note that the uptake of FDG in NHL is related to its pathological type; DLBCL and FL typically exhibit high FDG uptake, while MZL, MCL, and small lymphocytic lymphoma(SLL) usually show moderate to low FDG uptake. This variability results in differences in the diagnostic accuracy of 18F-FDG PET depending on the subtype of NHL. Additionally, approximately 11% of MM patients may present with false-negative FDG imaging, which could be attributed to factors such as small lesion size, a lower proliferation rate of clonal plasma cells, or hexokinase deficiency. Furthermore, physiological or inflammatory uptake of 18F-FDG can sometimes interfere with the detection of MM lesions.

In summary, early diagnosis before treatment, precise staging, and post-treatment prognostic stratification, as well as the detection of residual tumor metabolic activity, represent significant challenges in the diagnosis and treatment of NHL and MM. The use of 68Ga-pentixafor PET/MR allows for non-invasive visualization of CXCR4 expression in vivo, demonstrating high sensitivity for NHL and MM with low FDG uptake. This capability enhances diagnostic accuracy and facilitates precise staging, contributing to the development of personalized treatment plans and ultimately improving patient outcomes. Through the implementation of this project, the investigators aim to introduce new technologies in the management of NHL and MM patients, providing more effective diagnostic and therapeutic options.