This prospective, single-center, open-label exploratory diagnostic study aims to evaluate the safety, feasibility, and diagnostic performance of the novel Sortilin-targeted PET tracer 68Ga-SorB in patients with solid tumors. Eligible participants with confirmed or suspected melanoma, hepatocellular carcinoma, lung cancer, pancreatic cancer, breast cancer, or ovarian cancer will undergo 68Ga-SorB PET/CT imaging. The imaging findings will be compared with standard-of-care 18F-FDG PET/CT, using pathology results and/or clinical follow-up as the reference standard. The primary objectives are to evaluate the safety and tolerability of 68Ga-SorB, assess imaging feasibility, and characterize tumor uptake using quantitative PET parameters, including SUVmax and tumor-to-background ratio (TBR). Secondary exploratory objectives include comparing lesion detection between 68Ga-SorB PET/CT and 18F-FDG PET/CT, assessing diagnostic sensitivity and specificity, evaluating imaging characteristics across different tumor types, and exploring the correlation between Sortilin expression and tracer uptake. This study will provide preliminary clinical evidence supporting the development of Sortilin-targeted molecular imaging and future theranostic applications.
Background Sortilin is a type I transmembrane receptor belonging to the VPS10 receptor family. It is highly expressed in a variety of malignancies, including melanoma, hepatocellular carcinoma, lung cancer, pancreatic cancer, breast cancer, and ovarian cancer, while showing relatively low expression in most normal tissues. Due to its tumor-specific expression pattern and efficient receptor-mediated internalization, Sortilin has emerged as a promising molecular target for cancer imaging and targeted theranostic applications. Although \^18F-FDG PET/CT is widely used for oncologic imaging, its diagnostic performance may be limited by nonspecific uptake in inflammatory lesions, resulting in false-positive findings. Therefore, a more tumor-specific PET tracer may improve lesion detection and diagnostic accuracy. Study Design This is a prospective, single-center, open-label, exploratory diagnostic imaging study designed to evaluate the clinical performance of the novel Sortilin-targeted PET radiotracer \^68Ga-SorB. Approximately 40-50 adult patients with confirmed or suspected melanoma, hepatocellular carcinoma, lung cancer, pancreatic cancer, breast cancer, pancreatic cancer, or ovarian cancer will be enrolled. All participants will undergo \^68Ga-SorB PET/CT imaging according to the study protocol. Standard-of-care \^18F-FDG PET/CT performed within the predefined time window will be used as the comparator whenever available. Histopathological findings and/or clinical and imaging follow-up will serve as the reference standard for evaluating diagnostic performance. Study Objectives The primary objectives are to evaluate the safety and tolerability of \^68Ga-SorB, assess imaging feasibility, and characterize tracer biodistribution and tumor uptake using quantitative PET parameters, including SUVmax and tumor-to-background ratio (TBR). Secondary exploratory objectives include comparison of lesion detection between \^68Ga-SorB PET/CT and \^18F-FDG PET/CT, estimation of diagnostic sensitivity, specificity, and accuracy, evaluation of tracer uptake across different tumor types, assessment of the association between Sortilin expression and imaging parameters, and exploration of the potential clinical value of \^68Ga-SorB PET/CT in tumor diagnosis and staging. Study Significance This exploratory clinical study is expected to generate preliminary evidence regarding the safety, feasibility, and diagnostic performance of \^68Ga-SorB PET/CT in patients with solid tumors. The results may support further multicenter validation studies and facilitate the clinical development of Sortilin-targeted molecular imaging and future theranostic strategies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
50
Participants will receive a single intravenous administration of 68Ga-SorB (approximately 3.7 MBq/kg), followed by whole-body PET/CT imaging approximately 60 minutes after injection. The imaging findings will be compared with clinically indicated 18F-FDG PET/CT and reference standard findings to evaluate the safety, feasibility, biodistribution, tumor uptake, and exploratory diagnostic performance of 68Ga-SorB PET/CT.
Peking University Third Hospital
Beijing, Beijing Municipality, China
RECRUITINGIncidence of adverse events related to 68Ga-SorB PET/CT
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) related to administration of 68Ga-SorB, graded according to CTCAE.
Time frame: From tracer administration until completion of the imaging visit (approximately 24 hours).
Successful completion of 68Ga-SorB PET/CT imaging
Proportion of participants completing 68Ga-SorB PET/CT with evaluable image quality.
Time frame: At completion of PET/CT imaging (approximately 60 minutes after tracer injection)
Tumor uptake of 68Ga-SorB measured by SUVmax
Maximum standardized uptake value (SUVmax) of target lesions measured on 68Ga-SorB PET/CT.
Time frame: At PET/CT imaging (approximately 60 minutes after tracer injection)
Lesion detection rate on 68Ga-SorB PET/CT
Detection rate of reference standard-confirmed primary and metastatic tumor lesions visually identified on 68Ga-SorB PET/CT. Lesion detection will be assessed by lesion-based visual interpretation of 68Ga-SorB PET/CT images by nuclear medicine physicians. The detection rate will be calculated as the percentage of reference standard-confirmed lesions detected on 68Ga-SorB PET/CT. The reference standard will include pathology, clinical diagnosis, and/or imaging follow-up, as applicable.
Time frame: At completion of 68Ga-SorB PET/CT imaging, with reference-standard adjudication up to approximately 3 months after imaging.
Cohen's kappa coefficient for lesion detection agreement between 68Ga-SorB PET/CT and 18F-FDG PET/CT
Agreement in lesion detection between 68Ga-SorB PET/CT and clinically indicated 18F-FDG PET/CT. For each evaluable lesion, detection status will be recorded as detected or not detected on each PET/CT modality based on lesion-based visual image interpretation by nuclear medicine physicians. Agreement between the two PET/CT modalities will be assessed using Cohen's kappa coefficient with 95% confidence interval. Unit of Measure: Cohen's kappa coefficient, unitless.
Time frame: Within 2 weeks after completion of both PET/CT examinations.
Diagnostic sensitivity of 68Ga-SorB PET/CT for lesion detection
Diagnostic sensitivity of 68Ga-SorB PET/CT for lesion detection will be calculated using pathology, clinical diagnosis, and/or imaging follow-up as the reference standard. Lesion detection will be assessed by lesion-based visual interpretation of 68Ga-SorB PET/CT images by nuclear medicine physicians. Unit of Measure: Percentage.
Time frame: Within approximately 3 months after PET/CT imaging, following completion of pathology assessment, clinical diagnosis, and/or imaging follow-up.
Tumor SUVmax on 68Ga-SorB PET/CT by tumor type
Maximum standardized uptake value of tumor lesions on 68Ga-SorB PET/CT across different tumor types, including malignant melanoma, hepatocellular carcinoma, lung cancer, breast cancer, pancreatic cancer, and ovarian cancer, as applicable. SUVmax will be measured on fused PET/CT images using ROI/VOI delineation. Unit of Measure: Unitless standardized uptake value.
Time frame: At completion of 68Ga-SorB PET/CT imaging, approximately 60 minutes after tracer administration.
Correlation between Sortilin expression H-score and 68Ga-SorB PET/CT uptake parameters
Correlation between Sortilin expression in pathological tumor specimens and quantitative 68Ga-SorB PET/CT uptake parameters, including SUVmax and tumor-to-background ratio. For participants with available tissue samples, Sortilin expression will be measured by immunohistochemistry and reported as an H-score. SUVmax and tumor-to-background ratio will be measured on fused PET/CT images using ROI/VOI delineation. Correlation will be assessed using Pearson correlation analysis or Spearman rank correlation analysis, as appropriate. Unit of Measure: Correlation coefficient, unitless. Underlying Variable Units: Sortilin H-score, score range 0-300; SUVmax, unitless standardized uptake value; tumor-to-background ratio, unitless ratio.
Time frame: Within approximately 3 months after PET/CT imaging, following completion of pathological assessment.
Percentage of participants with a change in clinical diagnosis or tumor staging after 68Ga-SorB PET/CT
Percentage of participants whose clinical diagnosis or tumor staging changes after review of 68Ga-SorB PET/CT findings compared with the pre-PET/CT assessment based on standard imaging and clinical information. Changes in clinical diagnosis or tumor stage will be determined by investigator review of available clinical, imaging, pathological, and follow-up information. Unit of Measure: Percentage of participants.
Time frame: Within approximately 3 months after 68Ga-SorB PET/CT imaging.
Diagnostic specificity of 68Ga-SorB PET/CT for lesion detection
Diagnostic specificity of 68Ga-SorB PET/CT for lesion detection will be calculated using pathology, clinical diagnosis, and/or imaging follow-up as the reference standard. Lesion detection will be assessed by lesion-based visual interpretation of 68Ga-SorB PET/CT images by nuclear medicine physicians. Unit of Measure: Percentage.
Time frame: Within approximately 3 months after PET/CT imaging, following completion of pathology assessment, clinical diagnosis, and/or imaging follow-up.
Diagnostic accuracy of 68Ga-SorB PET/CT for lesion detection
Diagnostic accuracy of 68Ga-SorB PET/CT for lesion detection will be calculated using pathology, clinical diagnosis, and/or imaging follow-up as the reference standard. Lesion detection will be assessed by lesion-based visual interpretation of 68Ga-SorB PET/CT images by nuclear medicine physicians. Unit of Measure: Percentage.
Time frame: Within approximately 3 months after PET/CT imaging, following completion of pathology assessment, clinical diagnosis, and/or imaging follow-up.
Positive predictive value of 68Ga-SorB PET/CT for lesion detection
Positive predictive value of 68Ga-SorB PET/CT for lesion detection will be calculated using pathology, clinical diagnosis, and/or imaging follow-up as the reference standard. Lesion detection will be assessed by lesion-based visual interpretation of 68Ga-SorB PET/CT images by nuclear medicine physicians. Unit of Measure: Percentage.
Time frame: Within approximately 3 months after PET/CT imaging, following completion of pathology assessment, clinical diagnosis, and/or imaging follow-up.
Negative predictive value of 68Ga-SorB PET/CT for lesion detection
Negative predictive value of 68Ga-SorB PET/CT for lesion detection will be calculated using pathology, clinical diagnosis, and/or imaging follow-up as the reference standard. Lesion detection will be assessed by lesion-based visual interpretation of 68Ga-SorB PET/CT images by nuclear medicine physicians. Unit of Measure: Percentage.
Time frame: Within approximately 3 months after PET/CT imaging, following completion of pathology assessment, clinical diagnosis, and/or imaging follow-up.
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