Abstract
241958
Introduction: Prostate-specific membrane antigen (PSMA) is overexpressed on almost all types of prostate cancer (PCa) cells, making it an ideal target for the diagnosis and treatment of PCa.PET with PSMAligands plays an important role in the localization and diagnosis of intraprostatic lesions.PSMAPET-guided targeted biopsy has improved the detection rate of PCa to a certain extent.However, there are still some patients with PSMA-positive lesions on PSMAPET imaging who were initially negative on their first biopsy and only confirmed to have PCa after a second biopsy.18F and 68Galabeled PSMA are the most commonly used PET tracers in clinical research,but they have disadvantages such as short half-lives and expensive examination costs.In this study, our objective is to develop a novel single-photon emitting radiopharmaceutical, 123I-PSMA-7, for SPECT/CT imaging and real-time detection of PCa samples during prostate biopsy procedures.
Methods: We synthesized a high-affinity probe, 123I-PSMA-7, and evaluated its purity, stability, safety, and binding affinity to PSMA in 22Rv1 (PSMA+) and PC3 (PSMA-) tumor-bearing mice.In this prospective study with ethical support, we included 10 suspected PCa patients who underwent MRI or PSMAPET/CT examination prior to prostate biopsy. In these 10 patients, 5 were injected with 185MBq of 123I-PSMA-7, while the other 5 were injected with 55MBq of 123I-PSMA-7. Prostate biopsies were performed approximately 24 hours after injection. During the prostate biopsyprocedure, the radioactive activity of each biopsysample was measured using a gamma counter by counts per minute (CPM). Additionally, we recruited 3 patients to evaluate the potential of 123I-PSMA-7 SPECT/CT imaging for detecting PCa.
Results: 123I-PSMA-7 has a purity of over 95% within 24 hours, which meets the requirements for injection.Acute toxicity experiments have demonstrated that 123I-PSMA-7 does not cause damage to major tissues and organs. Micro-SPECT imaging of 123I-PSMA-7 in mice is consistent with biological distribution, indicating a high concentration of 123I-PSMA-7 in the 22Rv1 tumor. The maximum ratio between the tumor and muscle after 24 hours is approximately 50. These experiments ensure the feasibility of real-time targeted biopsy and PSMASPECT/CT imaging. In those five patients who received injections of 185MBq of 123I-PSMA-7, a total of 55 prostate biopsycores were performed. Using pathological diagnosis as the gold standard, 18 cores were positive for PCa; The CPM in the prostate cancer group was significantly higher than that in the non-prostate cancer group (714±547 vs 4345±3547, P<0.001); The AUC (area under the curve) of the ROC (receiver operating characteristic) analysis was 0.97, with a critical value of 1312. The sensitivity was 94.40% and the specificity was 91.90%.In those five patients who received injections of 55MBq of 123I-PSMA-7, a total of 55 prostate biopsycores were performed, and 10cores were positive for PCa; The CPM in the PCa group was significantly higher than that in the non-PCa group (153±112 vs 2446±1622, P<0.001); The AUC of the ROCanalysis was 1, with a critical value of 490; The sensitivity was 100% and the specificity was 100%.When the injection dose of 123I-PSMA-7 in patients was increased to 370 MBq, we achieved better SPE/CT imaging results, which were consistent with the pathological findings.
Conclusions: Through the assistance of the novel probe 123I-PSMA-7, accurate identification of benign and malignant lesions can be achieved during the process of prostate biopsy by real-time measurement of the sample radioactivity.This method can enhance the confidence of the operator, potentially increase the detection rate of PCa, and reduce the chances of repeated biopsies.Additionally, 123I-PSMA-7 SPECT/CT can provide satisfactory imaging results when the injection dose reaches 370MBq.