PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Biodistribution and preparation of technetium-99m-labeled D-D3 monoclonal antibody against pro-gastrin-releasing peptide (31₋98) in mice.

BACKGROUND: We previously reported that iodine-131((131)I)-labeled anti-pro-gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer (SCLC) xenografts. However, (131)I-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72 - 96 hours after injection. The aims of this study were to radiolabel anti-ProGRP(31-98) D-D3 monoclonal antibody with technetium-99m ((99m)Tc) and to investigate the biodistribution of this antibody in healthy ICR mice. METHODS: D-D3 was labeled with (99m)Tc via the 2-mercaptoethanol reduction method. (99m)Tc-D-D3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of (99m)Tc-D-D3 was determined with cell conjugation assays. (99m)Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram (%ID/g). RESULTS: The labeling rate and the radiochemical purity of (99m)Tc-D-D3 were (73.87 ± 2.89)% and (94.13 ± 4.49)%, respectively. The immunobinding rates of (99m)Tc-D-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were (81.2 ± 2.37)% and (24.3 ± 1.46)%, respectively. The distribution data of normal ICR mice demonstrated that (99m)Tc-D-D3 was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle. CONCLUSIONS: (99m)Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. (99m)Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, (99m)Tc-D-D3 is conducive to the radioimmunoimaging of SCLC.

[Values of (99m)TcO(-)(4)thyroid imaging plus ultrasonography in the differential diagnoses of thyroid nodules].

OBJECTIVE: To evaluate the diagnostic values of (99m)TcO(-)(4) thyroid imaging plus ultrasonography in the differentiation of benign and malignant thyroid nodules. METHODS: (99m)TcO(-)(4) thyroid imaging and ultrasonography were performed for 114 patients with 125 thyroid nodules. And the examination results were compared with the post-operative pathological findings. RESULTS: (1) Among 125 thyroid nodules, there were thyroid adenoma (n = 64, 51.2%), thyroid cancer (n = 30, 24.0%) and other thyroid diseases (n = 31, 24.8%). On thyroid images, 73.6% of them were of cold nodules. And among these cold nodules, 25.0% were of thyroid cancer. Among the ultrasonic results, 125 nodules were predominantly of solid nodules and mixed solid and cystic nodules while the malignant rate of solid nodules was the highest. (2) The malignant rate of solid cool or cold nodules was greater than those of mixed solid and cystic cool or cold nodules (P < 0.005). (3)In solid cool or cold nodules with a diameter of ≥ 2.0 cm, thyroid cancer accounted for 62.5%. CONCLUSION: The combination of (99m)TcO(-)(4) thyroid imaging and ultrasonography may help to evaluate the (99m)TcO(-)(4) uptaking functions of thyroid nodules so that it plays an important role in the differentiation of benign and malignant thyroid nodules.