Ascorbic Acid Analog 6-Deoxy-6-¹⁸F-Fluoro-l-Ascorbic Acid PET Imaging of 23 Various Cancer Types

High-dose ascorbic acid (AA) has shown promise as an adjunctive treatment for various cancers because of its prooxidant cytotoxicity at high concentrations and its multitargeting effects. However, identifying patients who may benefit from AA treatment remains an unmet need, as the therapeutic efficacy of AA is controversial. In this study, we aimed to use an AA analog-6-deoxy-6-¹⁸F-fluoro-l-AA (¹⁸F-FAA)-as a PET tracer and evaluate its uptake in various cancers, exploring its potential clinical application. Methods: This prospective study enrolled 116 patients with histopathologically confirmed malignant tumors who underwent ¹⁸F-FAA PET/CT. Tumors were quantitatively analyzed using the SUV_max, SUV_peak, and tumor-to-background ratio. Results: In total, 23 types of malignant tumors were assessed for their uptake of ¹⁸F-FAA, which was divided into tertiles using SUV_max percentiles. The highest uptake was observed in pheochromocytoma and paraganglioma, glioblastoma, and specific epithelial malignancies (e.g., nasopharyngeal, thyroid, and prostate carcinomas), with a median SUV_max exceeding 12.7, whereas the lowest uptake was found in breast, gastric, bladder, colorectal, and pancreatic cancers (median SUV_max, <8.2). Moderate uptake was noted in melanoma, diffuse large B-cell lymphoma, endometrial cancer, ovarian cancer, non-small cell lung cancer, cervical cancer, tumors of unknown primary origin, germ cell tumors, renal cancer, esophageal cancer, salivary duct carcinoma, malignant peritoneal mesothelioma, and hepatocellular carcinoma. The SUV_peak of these tumors was consistent with these findings. Both primary tumors and metastatic lesions exhibited tumor-specific degrees of ¹⁸F-FAA uptake and image contrast, with higher uptake in metastatic lesions (median SUV_max, 8.1 vs. 9.5, respectively; P = 0.026; tumor-to-background ratio, 12.9 vs. 14.9, respectively; P = 0.045). Conclusion: ¹⁸F-FAA PET/CT demonstrated distinct uptake characteristics across various tumor types and may provide new opportunities for the noninvasive assessment of tumor AA uptake characteristics and AA-based therapy.