Clinical PET Imaging Evaluation of 68Ga-NB381 Probe in Multiple Myeloma

Multiple myeloma (MM) predominantly affects the elderly, often presenting insidiously and with a rising incidence rate. Current diagnostic methods primarily rely on invasive bone marrow biopsies, which can lead to false-negative results if the biopsy site is improperly chosen. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for this disease. Addressing the limitations in specificity and sensitivity of traditional PET imaging agents, this project is dedicated to developing a new type of nanobody PET/CT imaging probe, 68Ga-NB381, which possesses high affinity and targets CD38. This probe, which is an intellectual property of our institution, aims to enhance the accuracy and specificity of early MM diagnosis. In terms of clinical evaluation, the project will implement a comprehensive assessment process including case selection, collection of baseline information, high-precision imaging, expert-level image interpretation, and follow-up studies, comparing directly with traditional 18F-FDG imaging to thoroughly verify the specificity and safety of 68Ga-NB381. This lays the groundwork for the clinical translation of this radiopharmaceutical in China. Furthermore, the project contributes to formulating more effective precision treatment plans based on CD38 expression levels and provides evidence for monitoring the therapeutic effects of daratumumab, a drug also targeting CD38. This makes the project of significant academic value and clinical importance, thus promoting the development of personalized treatment strategies.

Early Phase I Evaluation of 64Cu-LLP2A for Imaging Multiple Myeloma

The investigators are performing a trial with goals to demonstrate the feasibility of imaging multiple myeloma (MM) patients with 64Cu-LLP2A-positron emission tomography (PET)/magnetic resonance (MR). The investigators suggest that 64Cu-LLP2A will allow for an accurate molecular imaging of MM lesions, which will have an important impact on early stage disease detection and in the long term on the initiation and choice of therapy in these patients.

18F-Fluorocholine (FCH) Versus 18F-Fluorodesoxyglucose (FDG) PET/CT in Detection of Lesions in Patients With Multiple Myeloma

Hybrid positron emission tomography/computed tomography (PET/CT) has now become available to detect tumors in patients with multiple myeloma. The radioactive glucose 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but findings suggest that PET/CT reveal more lesions when using FCH. In this study, FDG is compared with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of multiple myeloma lesions at time of initial extension assessment. The principal objective of this sudy is to compare the number of suspected hypermetabolic foci of myeloma detected by 18F-fluorocholine PET and by 18F-fluorodeoxyglucose PET during the initial extension assessment.

A Diagnostic Study of CD38-Targeted ImmunoPET of Myeloma: Phase 2 Trial of Clinical Applications

Evaluation of myeloma disease burden is currently suboptimal. This limits treatment planning and evaluation of residual disease following treatment. 89Zr-DFO-daratumumab is a novel immunoPET tracer, designed to detect CD38 on myeloma cells and allow visualization of myeloma in a PET scanner. A phase I study of 89Zr-DFO-daratumumab demonstrated safety and successful visualization of myeloma with 89Zr-DFO-daratumumab. This will be a phase II study of 89Zr-DFO-daratumumab to evaluate potential clinical applications of this novel imaging agent.

Phase 1 Trial of 111Indium/225Actinium-DOTA-Daratumumab in Patients With Relapsed/Refractory Multiple Myeloma

This phase I trial tests the safety, side effects, and best dose of actinium Ac 225-DOTA-daratumumab (225Ac-DOTA-daratumumab) in combination with daratumumab and indium In 111-DOTA-daratumumab (111In-DOTA-daratumumab) in treating patients with multiple myeloma that does not respond to treatment (refractory) or that has come back (recurrent). Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab are forms of radioimmunotherapy in which a monoclonal antibody, daratumumab, has been linked to a radiotracer to allow for targeted delivery of the treatment to cancer cells. Giving all three together may kill more cancer cells.

A Head-to-head Comparative Study of 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT Imaging in Multiple Myeloma

Multiple myeloma (MM) is the second most common hematological malignancy and is still incurable. Positron emission tomography/computed tomography (PET/CT) has been used to diagnose, assess treatment response, and predict prognosis in MM. 18F-fluorodeoxyglucose (FDG) is the most widely used radiotracer, but there is heterogeneous uptake in MM, that is, uptake is negative in some myeloma cells. There are currently reports of cases with strong uptake of prostate-specific membrane antigen (PSMA) PET/CT in MM. Therefore, this preliminary study was designed to compare the imaging results of 18F-PSMA-1007 PET/CT and 18F-FDG PET/CT, and to evaluate the additional value of 18F-PSMA-1007 PET/CT to 18F-FDG PET/CT in MM.

Pilot PET Imaging Study of [89Zr]DFO-YS5 for Detecting CD46 Positive Malignancy in Multiple Myeloma

This phase I trial tests the safety of [89Zr]DFO-YS5 positron emission tomography (PET) imaging and how well it works to detect CD46 positive cancer cells in patients with multiple myeloma. [89Zr]DFO-YS5 is an imaging agent called a radiopharmaceutical tracer. A radiopharmaceutical tracer uses a small amount of radioactive material that is injected into a vein to help image different areas of the body. [89Zr]DFO-YS5 targets a specialized protein called CD46, which is in certain multiple myeloma cancer cells, and [89Zr]DFO-YS5 PET scans may improve detection of multiple myeloma.

Clinical PET Imaging Evaluation of 68Ga-NB381 Probe in Multiple Myeloma

Multiple myeloma (MM) commonly occurs in the elderly and often remains undetected until it reaches an advanced stage. With the aging population in China, the incidence of MM is on the rise, now surpassing that of acute leukemia. Clinically, MM is characterized by bone destruction and lacks specificity; diagnosis primarily relies on bone marrow biopsies that detect an increase in clonal plasma cells, which are invasive and can yield false-negative results if the biopsy site is improperly selected. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for MM. As the incidence of malignant tumors in China continues to increase, so does the clinical demand for radiopharmaceuticals. Addressing the limitations in the targeting of 18F-FDG in PET imaging, the development of new targeted nuclear medicine molecular probes is of significant academic value and clinical importance, particularly in monitoring the therapeutic effects of the CD38-targeted nanobody NB381, which offers unique advantages. This project uses a nanobody with high affinity for CD38 as the targeting moiety for the radiopharmaceutical, exploring the diagnostic efficiency of 68Ga-NB381 in patients with MM exhibiting high CD38 expression. This not only provides a basis for the early diagnosis of MM but also allows for the formulation of effective precision treatment strategies based on the CD38 expression profile in MM patients. 68Ga-NB381, a new CD38-targeted molecular probe labeled with 68Ga, can be used for the diagnosis and research of various malignancies expressing high levels of CD38, including MM. The probe is conjugated with 68Ga3+ using TOHP as a bifunctional chelator, with a simple labeling process that does not require purification, offering high in-vivo stability and significant radioactive accumulation in tumor sites in mouse models, resulting in superior imaging outcomes. This project will complete the automation of the 68Ga-NB381 labeling process and conduct quality control studies on the resulting radiopharmaceutical injection solution, establishing quality standards for this new PET probe and laying the foundation for its clinical translation in China. The project aims to provide 68Ga-NB381 PET/CT imaging studies to support the early diagnosis of CD38 high-expression malignancies, the formulation of treatment plans, and the assessment of therapeutic efficacy.