Preliminary Clinical Investigation of [68Ga] Ga or [177Lu] Lu-Labeled DOTA-IBA for the Diagnosis and Treatment of Bone Metastasis

Introduction: This study conducts a comprehensive analysis of the therapeutic efficacy and adverse reactions associated with [⁶⁸Ga] Ga-DOTA-IBA and [¹⁷⁷Lu] Lu-DOTA-IBA in the context of advanced-stage tumor-related bone metastasis. DOTA-IBA, an enhanced phosphinate, is radiolabeled with gallium-68, serving as a diagnostic imaging agent to facilitate visual assessments of bone metastatic lesions. It is instrumental in patient selection for tailored therapeutic interventions. Post-labeling with lutetium-177, DOTA-IBA is employed for radiotherapeutic interventions on bone metastatic lesions, followed by SPECT/CT imaging to evaluate drug distribution and dosimetry. Preliminary trials have evidenced a therapeutic duration of ¹⁷⁷Lu exceeding 28 days.

Methods: This investigation recruited patients in advanced stages of tumor-related bone metastasis with suboptimal or ineffective clinical outcomes for an integrated ⁶⁸Ga/¹⁷⁷Lu-DOTA-IBA study. Biochemical and hematological determinations were conducted before patient examinations. On the day of examination, patients received a standard intravenous injection of [⁶⁸Ga] Ga-DOTA-IBA at a dosage of 0.05 mCi/kg, with PET/CT imaging performed 2 hours post-administration. Evaluation of patient suitability for [¹⁷⁷Lu] Lu-DOTA-IBA treatment was undertaken by experienced nuclear medicine practitioners based on patient conditions, CT characteristics of lesions (density, size, etc.), and PET features (SUVmax, MTV, etc.). Eligible patients received 2-4 treatment cycles involving slow intravenous infusion of 30 mCi [¹⁷⁷Lu] Lu-DOTA-IBA. Following the administration of [¹⁷⁷Lu] Lu-DOTA-IBA, patients underwent comprehensive whole-body planar imaging, including anterior and posterior views, and SPECT/CT imaging approximately 1，2 and 7 days later to assess biodistribution and dosimetry. Additionally, a subset of patients underwent imaging 28 days post-drug injection. Evaluation of treatment efficacy and adverse events was facilitated through an analysis of changes in clinical symptoms, imaging comparisons, and biochemical indicators.

Results: As of the current state, [⁶⁸Ga] Ga-DOTA-IBA imaging has been conducted in 811 patients, and [¹⁷⁷Lu] Lu-DOTA-IBA treatment has been administered to 210 patients. Panel A-C in Figure show [⁶⁸Ga] Ga-DOTA-IBA PET/CT MIP images of patients with pulmonary carcinoma, isolated plasma cell tumor, and prostate cancer before and after therapy, respectively. The [⁶⁸Ga] Ga/[¹⁷⁷Lu] Lu-DOTA-IBA drugs have demonstrated favorable tolerability, with no severe drug-related adverse events observed in the cases studied. In a limited number of cases, mild to moderate leukopenia was recorded among the treated patients. [⁶⁸Ga] Ga-DOTA-IBA is predominantly excreted via renal pathways, with minimal distribution in normal bone tissues. Similarly, [¹⁷⁷Lu] Lu-DOTA-IBA is primarily excreted via renal pathways, exhibiting uptake and prolonged retention in areas identified as positive by [⁶⁸Ga] Ga-DOTA-IBA PET/CT. Bone pain relief was seen in 84% of cases, the treatment demonstrated significant therapeutic effects in certain metastatic lesions, as evidenced by imaging findings such as osteogenic reactions.

Conclusions: The current treatment cases support the safety of [⁶⁸Ga] Ga-DOTA-IBA PET/CT for disease imaging and the selection of suitable patients for tailored therapeutic interventions. [¹⁷⁷Lu] Lu-DOTA-IBA effectively uptakes and persists in regions identified as positive by [⁶⁸Ga] Ga-DOTA-IBA PET/CT. The integrated diagnostic and therapeutic approach of [⁶⁸Ga] Ga/[¹⁷⁷Lu]Lu-DOTA-IBA is poised to make a significant contribution to the treatment of bone pain and bone metastasis in cancer patients.

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