Preparation and SPECT/CT Imaging of 177Lu-Labeled Peptide Nucleic Acid (PNA) Targeting CITED1: Therapeutic Evaluation in Tumor-Bearing Nude Mice.

PURPOSE: The expression of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 1 (CITED1) is upregulated in papillary thyroid carcinoma (PTC) and mediates cell proliferation and migration. To facilitate early diagnosis and monitoring of recurrent or metastatic PTC, we designed 177Lu-labeled antisense peptide nucleic acid (PNA) targeting CITED1 mRNA to evaluate the therapeutic potential, while analyzing its distribution in nude mice and the characteristics withsingle-photon emission-computed tomography/computed tomography (SPECT/CT) imaging. MATERIALS AND METHODS: 177Lu-DOTA-anti-CITED1-PNA (177Lu-asPNA) was obtained by indirect labeling. High-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used to determine the labeling rate and radiochemical purity. The stability of 177Lu-asPNA was evaluated by TLC, and the radioactivity count was measured by a γ counter to calculate its uptake capacity in K1 cells. To analyze the distribution of 177Lu-asPNA in body tissues and organs of nude mice, static single-photon emission-computed tomography (SPECT) imaging and SPECT/CT image fusion were performed. Then, the therapeutic effects of probes were explored by tumor growth curves and survival analysis. RESULTS: Our probe showed a radiochemical purity of 96.5±0.15% at 1 hr and specific activity of 8.7±0.53 MBq/µg. The uptake rate in the 177Lu-asPNA group was much higher than that in the 177Lu-DOTA-nonsense-PNA (177Lu-nonsense-PNA) and 177Lu-DOTA groups (P<0.05). The biological distribution showed that the tumor/muscle ratio was at its highest at 24 h (4.98±0.34) post-inoculation, with SPECT/CT imaging showing clear tumor development. By measuring tumor volume of tumor-bearing nude mice, the 177Lu-asPNA group showed a significant difference in tumor size 9 days after injection (P < 0.05). Kaplan-Meier survival curves showed that the overall survival rate in the 177Lu-asPNA group was significantly different from those in the DOTA-anti-CITED1-PNA (asPNA) and saline groups (P = 0.002, log-rank test). CONCLUSION: 177Lu-asPNA was developed successfully, showing a high labeling rate and good stability. SPECT/CT imaging demonstrated tumor growth in nude mice, which was effectively inhibited by our probe, thus prolonging survival.

The role of 18F-FCH PET/CT in patients with uremic hyperparathyroidism compared with 99mTc-sestaMIBI SPECT/CT and ultrasonography.

BACKGROUND: The aim of this study was to evaluate the diagnostic efficacy of 18F-fluorocholine (18F-FCH) PET/CT for uremic hyperparathyroidism (uHPT) compared to 99mTc-sestaMIBI SPECT/CT and ultrasonography (US). METHODS: A total of 17 uHPT patients with stage 5 chronic kidney disease (CKD) were prospectively enrolled. All patients underwent US, 99mTc-sestaMIBI SPECT/CT, and 18F-FCH within 2 months and received surgical treatment. Visual and quantitative methods were used for image analyses. Intraoperative localization and postoperative histological results of the reference standard as well as the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the three modalities were analyzed using Pearson's χ2 tests. In addition, the diagnostic efficacy of 18F-FCH PET/CT for uHPT was evaluated. The relationships between PET parameters and laboratory parameters were assessed using the Spearman correlation coefficient. RESULTS: A total of 63 parathyroid hyperplasia lesions were resected in 17 uHPT patients, and 53 lesions were detected using 18F-FCH PET/CT with no false-positive results. The sensitivity, specificity, accuracy, PPV, and NPV were 84.13%, 100%, 86.49%, 100%, and 52.38%, respectively. In comparison, the corresponding values for 99mTc-sestaMIBI SPECT/CT and US were 63.49%, 90.91%, 67.57%, 97.56%, and 30.30% and 61.90%, 81.82%, 64.86%, 95.12%, and 27.27%, respectively. The volume of hyper-functioning parathyroid glands was significantly different between lesions positive in 18F-FCH PET/CT and negative in 18F-FCH PET/CT (mean volume 1.36 ± 0.55 cm3 vs. 0.83 ± 0.26 cm3; P = 0.019). US misidentified intrathyroidal parathyroid hyperplasia as thyroid nodules in three patients, while 18F-FCH PET correctly identified the anatomy. No significant associations were observed between PET parameters and laboratory parameters in uHPT. CONCLUSION: 18F-FCH PET/CT was more sensitive and accurate for uHPT than 99mTc-sestaMIBI SPECT/CT and US, and had better preoperative diagnostic efficacy, particularly for lesions diagnosed as a thyroid nodule by US.

Extensive peritoneal implant metastases of malignant struma ovarii treated by thyroidectomy and 131I therapy: A case report.

RATIONALE: Malignant struma ovarii is extremely rare in the clinic. The diagnosis and modalities of treatment are still controversial. Here we describe a case of extensive peritoneal implant metastasis originating from malignant struma ovarii discovered 14 years after ovariectomy and chemotherapy. PATIENT CONCERNS: A 48-year-old female was admitted to our clinic due to hematochezia with a past history of left malignant struma ovarii. Enhanced computed tomography (CT) examination suggested multiple metastasis nodules in the abdomen and pelvic cavity. DIAGNOSES: Laparoscopy biopsy results of intraperitoneal nodules showed a metastasis of papillary thyroid carcinoma. While pathological examination after total thyroidectomy showed no definite malignant tumor component in the thyroid tissue. Finally, combined with the patient's past history of malignant struma ovarii, peritoneal implantation metastasis derived from the malignant struma ovarii was diagnosed. INTERVENTIONS: The patient was treated by total thyroidectomy and iodine 131 (I) therapy. Post-therapy iodine scan and the single-photon emission computed tomography/computed tomography (SPECT/CT) fusion image showed iodine uptake in the distal descending colon, sigmoid colon, rectal lesions, and a larger lesion in the liver. OUTCOME: After treatment, although the thyroid globulin remained at a high level 3 months after treatment, the patient's hematochezia was relieved. LESSONS: Therefore, thyroidectomy followed by adjuvant I treatment should be recommended in patients with malignant struma ovarii as metastatic risk is difficult to predict based on histopathologic examination.

Radioimmunoimaging with mixed monoclonal antibodies of nude mice bearing human lung adenocarcinoma xenografts.

The present study was conducted to evaluate radioimmunoimaging (RII) and in vivo distribution of mixed antibodies 99mTc-EGFR-mAb and 99mTc-CD44- mAb in nude mice bearing human lung adenocarcinoma xenografts. Single and mixed applications of the two radiolabeled monoclonal antibodies (mAbs) were compared. Direct labeling of 99mTc was applied to radiolabel the EGFR and CD44 mAbs. The properties of the radiolabeled antibodies were then characterized. RII and assessment of the distribution of the antibodies in nude mice bearing lung adenocarcinoma xenografts were achieved by applying separate and combined doses of 99mTc-EGFR-mAb and 99mTc-CD44-mAb. The labeling rates of 99mTc for EGFR-mAb and CD44-mAb were 91.5% ±3.8% and 92.3% ± 4.1% respectively, with specific activities of 2.8 and 2.9 MBq/µg, respectively, and radiochemical purities (RCP) of 96.5% and 96.2%. The radioactivity uptake of the combined application of both radiolabeled antibodies was clearly higher than with a single application of either alone. The relative values of target-to-nontarget (T/ NT) measured through the regional interest (ROI) technique were 5.59 ± 0.42 (mixed antibodies), 2.78 ±0.20 (99mTc-EGFR-mAb), and 2.28 ± 0.16 (99mTc-CD44-mAb) in the RII. The body distribution of the radiolabeled antibodies and their imaging results were basically identical. Application of the mixed antibodies with 99mTc- EGFR-mAb and 99mTc-CD44-mAb can increase the radioactivity uptake of tumor tissue, leading to more ideal target-to-nontarget ratios, and therefore superior results.

[Localization of sentinel lymph node with radionuclide in clinically N0 laryngeal and hypopharyngeal cancers].

OBJECTIVE: To analyze the characteristic of the radioactive lymph node with metastatic disease and to explore the method of the localization of sentinel lymph node (SLN) with radionuclide in N0 clinically laryngeal and hypopharyngeal cancer. METHODS: Fourty-five patients with T1-T4 and clinically N0 laryngeal and hypopharyngeal cancer were recruited. For each patient a peritumoral submucosal injection of 99mTc-labeled sulfur colloid (99mTc-SC) was performed and lymph node mapping was performed by lymphoscintigraphy two hours afterward. The SLN was localized by a handheld gamma probe intraoperatively 10-12 hours after the injection. All hot lymph nodes accumulating activity were harvested and initially termed sentinel nodes. Selective neck dissections were performed for all patients. The specimen of SLN was sent to the pathologist for the following analysis: formal paraffin embedded section, consecutive section and immunohistochemistry assay. The results was compared to the remaining lymphadenectomy specimen. Resection of the primary tumour depended on the location and the T classification. RESULTS: SLNs were identified in 41 of 45 patients with 51 necks, SLNs had occult metastases in 13 cases, 15 necks with SLN-positive of these 13 cases, there was one false negative case, they were found in non-SLNs of neck specimens. Each neck side was considered a single case. SLN identification rate was 92.7%, sensitivity was 93.7%, false-negative rate was 6.3%, and accuracy was 98.0%. In 11 (73.3%) of these SLN-positive necks, the SLN with the highest counts contained tumor; harvesting the first-three nodes with the highest radioactive counts, which could all patients with occult metastatic disease. CONCLUSIONS: Excision of the first-three SLNs with the highest radioactive counts can accurately judge the presence or absence of the cervical lymph nodes metastases in patients with the clinically N0 laryngeal and hypopharyngeal cancer.