68Ga-labeled WVP peptide as a novel PET probe for molecular biological diagnosis of unstable thoracic aortic aneurysm and early dissection: an animal study.

Objective: Type IV collagen (Col-IV) is a prospective biomarker for diagnosing and treating of unstable thoracic aortic aneurysm and dissection (TAAD). This study aims to evaluate the feasibility of 68Ga-labeled WVP peptide (68Ga-DOTA-WVP) as a novel Col-IV-targeted probe for TAAD biological diagnosis using PET/CT. Methods: WVP peptide was modified with bifunctional chelator DOTA for 68Ga radiolabeling. Immunohistochemical staining was used to evaluate the expression and location of Col-IV and elastin in aortas treated with 3-aminopropionitrile fumarate (BAPN) at different time points (0, 2, and 4 weeks). The imaging performance of 68Ga-DOTA-WVP was investigated using Micro-PET/CT in a BAPN-induced TAAD mouse model. The relationship between 68Ga-DOTA-WVP uptake in aortic lesions and the serum levels of TAAD-related biomarkers including D-dimer, C-reactive protein (CRP), and serum soluble suppression of tumorigenicity-2 (sST2) was also analyzed. Results: 68Ga-DOTA-WVP was readily prepared with high radiochemical purity and stability in vitro. 68Ga-DOTA-WVP Micro-PET/CT could detect Col-IV exposure of unstable aneurysms and early dissection in BAPN-induced TAAD mice, but little 68Ga-DOTA-WVP uptake was shown in the control group at each imaging time point. The differences of Col-IV expression and distribution of 68Ga-DOTA-WVP both in TAAD and control groups further verified the imaging efficiency of 68Ga-DOTA-WVP PET/CT. Additionally, a higher sST2 level was found in the imaging positive (n = 14) than the negative (n = 8) group (9.60 ± 1.14 vs. 8.44 ± 0.52, P = 0.014). Conclusion: 68Ga-DOTA-WVP could trace the exposure and abnormal deposition of Col-IV in enlarged and early injured aortas, showing a potential for biological diagnosis, whole-body screening, and progression monitoring of TAAD.

Radiolabeling LyP-1 peptide and preliminary biodistribution evaluation in mice bearing MDA-MB-435 xenografts.

BACKGROUND: Recent studies have shown the LyP-1 peptide can home to either tumor lymphatics or the tumor cells and be internalized by targeted cells. This study aimed to investigate the possibility of using Na(131)I labeled LyP-1 peptide as an imaging agent or a therapeutic radiopharmaceutical in breast carcinoma and its metastasis. METHODS: The 10-mer cyclic peptide contained the LyP-1 sequence (YCGNKRTRGC) was synthesized by the solid phase method. Disulfide bonds between the cysteines maintain the cyclic structure. The LyP-1 peptide was labeled with Na(131)I using the chloramine-T method. The [(131)I] LyP-1 peptide and a [(131)I] control peptide were injected via tail vein into nude mice bearing MDA-MB-435 tumor xenografts. Biodistribution and imaging results in vivo were obtained. RESULTS: The labeling efficiencies of LyP-1 peptide reached 80% ± 5% (n = 5). The radiochemical purity was about 96%. The radiochemical purity of the labeled compound remains 92% at 24 hours in human serum at 37°C. In the biodistribution studies, the [(131)I] LyP-1 peptide accumulated in the tumor to a higher level than in other organs. The [(131)I] LyP-1 peptide can successfully image the tumor in nude mice bearing MDA-MB-435 tumor xenografts. CONCLUSIONS: The LyP-1 peptide could be effectively labeled with Na(131)I and the labeled compound is stable in human serum at 37°C for 24 hours. The high specificity of [(131)I] LyP-1 peptide suggests it may be a promising new radiotracer for identifying tumors.

Study on biodistribution and imaging of radioiodinated arginine-arginine-leucine peptide in nude mice bearing human prostate carcinoma.

OBJECTIVE: To investigate the biodistribution and imaging of (131)I-labeled arginine-arginine-leucine (RRL) peptide in human prostate carcinoma bearing nude mice. METHODS: The 10-mer cyclic peptide containing the RRL sequence (YCGGRRLGGC) was synthesized by the solid-phase method. Disulfide bonds between the cysteines maintain the cyclic structure. Radioiodination of the RRL peptide was performed by the chloramine-T method. (131)I-labeled peptides were injected into the nude mice bearing human prostate carcinoma via a tail vein. Biodistribution and imaging results in vivo were obtained. RESULTS: The (131)I-labeling rate of RRL peptide was about 60%. The radiochemical purity was 96.5%. The radiochemical purity of the labeled compound remained 90.3% at 24 h in human blood serum at 37 degrees C. In the biodistribution studies, radiolabeled RRL peptide probe accumulated in the tumor to a level of approximately 2.52 and 0.65% injected dose per gram of tissue at 6 and 24 h after administration. The data for the (131)I-labeled control peptide were 0.73 and 0.06% ID/g at 6 and 24 h after administration. The ratios of radioactivity in tumors to radioactivity in blood at 1, 6, and 24 h after injection were about 0.32, 1.12, 1.30 for RRL peptide and 0.30, 0.37, 0.22 for control peptide. The ratios of radioactivity in tumors to radioactivity in muscle at 1, 6, 24 h after injection were about 1.40, 3.94, 9.08 for RRL peptide and 1.98, 2.89, 1.78 for control peptide. At 24 h after administration, the SPECT imaging obtained clearly showed a contrasting tumor on the right armpit of mice with high concentrations of radioactivity, and the surrounding background was very low. CONCLUSIONS: The results suggest that radioiodination of RRL peptide is feasible and that the labeled compound is stable in human blood serum. The (131)I-labeled RRL peptide shows high tumor uptake and good tumor-to-organ ratios that allow noninvasive visualization of tumors. The (131)I-labeled compound is valuable to detect tumors as molecular probe.