研究内容一
68Ga-DOTA-3PRGD2 与 18F-FDG PET/CT 检测腺样囊性癌 的比较
研究目的:腺样囊性癌(adenoid cystic carcinoma, ACC)是一种罕见的恶性肿瘤， 主要发生在分泌腺内，本研究的目的是探索靶向整合素 αvβ3 的以 DOTA 为螯合 基团、诊疗一体化探针 68Ga-DOTA-3PRGD2 在 ACC 诊断中的表现，评估 68Ga- DOTA-3PRGD2 与 18F-FDG PET/CT 在 ACC 中的检出能力和摄取特征，比较两 种显像剂的有效性。
研究方法:这项前瞻性研究招募了 30 名 ACC 患者(15 名男性，15 名女性;年 龄:22-70 岁，平均值±标准差:42 ± 12 岁)。所有入组的患者均进行了 68Ga- DOTA-3PRGD2 PET/CT 显像，其中有 18 名患者同时进行了 18F-FDG PET/CT 显 像，两次显像时间间隔不超过 48 小时，两次显像期间患者不能接受任何治疗。 图像的判读采用视觉分析及半定量分析，使用最大标准化摄取值(max standard uptake value, SUVmax)和平均标准化摄取值(mean standard uptake value, SUVmean)半定量分析来评估病灶的摄取情况。使用 SPSS 软件进行计算。所有 数据均以平均值±标准差表示。所有统计学检验均为双侧，P < 0.05 为具有统计显 著性。
研究结果:30 名患者均进行了 68Ga-DOTA-3PRGD2 PET/CT 检查，其中 14 名 (46.7%)患者有头颈部局部复发，18 名同时进行了 68Ga-DOTA-3PRGD2 PET/CT 和 18F-FDG PET/CT 检查的患者，10 名(55.6%)患者有头颈部局部复发，转移 部位最多的是肺，其次是骨、淋巴结、肝、胸膜和胸大肌。各部位病灶 68Ga-DOTA- 3PRGD2 PET/CT 的 SUVmax 和 SUVmean 范围分别为 1.0 - 8.0 和 0.7 - 6.8(平均 值±标准差:3.71 ± 1.54 和 2.53 ± 1.80)，头颈部局部复发病灶的 SUVmax 和 SUVmean 的范围分别为 2.5 - 5.5 和 1.3 - 3.4(平均值±标准差:3.77 ± 0.90 和 2.30 ± 0.66)，肺转移病灶的 SUVmax 和 SUVmean 的范围分别为 1.0 - 8.0 和 0.7 - 6.8 (平均值±标准差:3.34 ± 1.96 和 2.23 ± 1.82)，肝转移病灶的 SUVmax 和 SUVmean 的范围分别为 3.2 - 5.4 和 2 - 3.8(平均值±标准差:4.03 ± 1.19 和 2.63 ± 1.01)， 骨转移病灶的 SUVmax 和 SUVmean 的范围分别为 2.2 - 7.0 和 1.2 - 5.3(平均值 ±标准差:4.10 ± 1.39 和 3.20 ± 2.57)，淋巴结转移病灶的 SUVmax 和 SUVmean 的范围分别为 1.8 - 5.5 和 0.9 - 4.0(平均值±标准差:3.17 ± 1.24 和 1.90 ± 1.04)，
 胸膜转移病灶的 SUVmax 和 SUVmean 的范围分别为 2.1 - 7.0 和 1.2 - 5.7(平均 值±标准差:4.60 ± 2.45 和 3.40 ± 2.25)，胸大肌转移病灶的 SUVmax 和 SUVmean 分别为 2.60 和 1.60。18F-FDG PET/CT 检查检测出的全身各部位阳性病灶、肺转 移病灶和骨转移病灶的数量显著多于 68Ga-DOTA-3PRGD2 PET/CT(全身病灶数 量比:1491 vs 770，P < 0.001;肺转移病灶数量比:771 vs 564，P = 0.008;骨转 移病灶数量比:341 vs 105，P = 0.036)。全身病灶的 18F-FDG 的摄取程度显著 高于 68Ga-DOTA-3PRGD2(SUVmax 比:8.28 ± 5.45 vs 3.90 ± 1.62，P < 0.001; SUVmean 比:5.80 ± 4.65 vs 2.56 ± 1.45，P < 0.001)。头颈部局部复发病灶、肺 转移病灶和骨转移病灶的 18F-FDG 的摄取程度也显著超过 68Ga-DOTA-3PRGD2。 肝转移病灶和淋巴结转移病灶，虽然未达到统计学显著性差异，但也表现出了较 高的 18F-FDG 摄取程度。胸大肌转移病灶的 18F-FDG 摄取程度要高于 68Ga-DOTA- 3PRGD2。相反的，胸膜转移病灶 68Ga-DOTA-3PRGD2 的摄取值的平均值要高于 18F-FDG(18F-FDG vs 68Ga-DOTA-3PRGD2 SUVmax 比:3.95 ± 0.49 vs 4.55 ± 3.46; SUVmean 比:2.05 ± 0.35 vs 3.45 ± 3.18)。相关性分析结果显示，68Ga-DOTA- 3PRGD2 PET/CT 和 18F-FDG PET/CT 上肿瘤 SUVmax(r = 0.506，P < 0.001) 和 SUVmean 值呈正相关(r = 0.539，P < 0.001)。 研究结论:这项研究首次临床转化新型分子探针 68Ga-DOTA-3PRGD2 并应用于 ACC 的诊断中。18F-FDG PET/CT 和 68Ga-DOTA-3PRGD2 PET/CT 都是检测 ACC 的有前景的成像方式，68Ga-DOTA-3PRGD2 PET/CT 可以在特定临床情况下为 18F-FDG PET/CT 提供补充信息，对于识别全身肿瘤病灶、评估肿瘤的发展趋势 和潜在治疗靶点具有应用价值。

 研究内容二

177Lu 标记的 AB-3PRGD2 靶向治疗晚期整合素 αvβ3 阳性肿 瘤的首次人体安全性、药代动力学和剂量测定的研究
研究目的:整合素 αvβ3 在新生血管和各种肿瘤细胞中显著过表达。本研究旨在评 估靶向整合素 αvβ3 的新型放射性药物 177Lu-AB-3PRGD2 的安全性、药代动力学 和剂量测定。
研究方法:这项单中心、前瞻性的研究招募了 10 名患有不同恶性肿瘤的患者(3 名男性，7 名女性;年龄:23 - 70 岁，平均值±标准差:45 ± 16 岁;BMI:13.40 - 29.30 kg/m2，平均值±标准差:20.79 ± 5.13 kg/m2;8 名腺样囊性癌、1 名胆管细 胞癌和 1 名子宫平滑肌肉瘤)。在获得伦理审查委员会(institutional review board, IRB)批准和患者知情同意后，所有患者均在 177Lu-AB-3PRGD2 治疗前两周内进 行 68Ga-DOTA-3PRGD2 PET/CT 和 18F-FDG PET/CT 检查，68Ga-DOTA-3PRGD2 和 18F-FDG PET/CT 两种检查的时间间隔在 48 小时内，静脉输注 177Lu-AB- 3PRGD2(1565.84 ± 78.15 MBq，42.32 ± 2.11 mCi)进行治疗。所有患者在治疗 后 3、24、48、72、96、120 和 168 小时接受全身平面和 SPECT/CT 扫描。在治 疗后 5 分钟、3 小时、24 小时、72 小时和 168 小时采集静脉血样进行放射性测 量。随访时间为 6 - 8 周，期间收集临床数据和实验室检查，包括患者的主观健 康情况、治疗前和治疗后每两周的血常规检查、肝功能和肾功能检查，根据不良 事件通用术语评价标准 5.0(Common Toxicity Criteria for Adverse Events, CTCAE V5.0)对不良事件进行分级。在治疗后 6 至 8 周重复 68Ga-DOTA-3PRGD2 和 18F- FDG PET/CT 检查以进行疗效评估。Hermes 软件用于推导器官的吸收剂量、全 身有效剂量和停留时间。使用 SPSS 软件进行计算。所有数据均以平均值±标准 差表示。所有测试均为双侧测试，P 值<0.05 被认为具有统计学意义。 研究结果:177Lu-AB-3PRGD2 给药安全且耐受性良好，无明显急性不良事件或 4/5 级毒性。3 例患者出现不良反应，包括转氨酶升高和血红蛋白减少。实验室 评估显示，治疗前后白细胞(治疗前:6.37 ± 1.89×109/L，治疗后:5.92 ± 1.69×109g/L，P = 0.495)、血红蛋白(治疗前:126.60 ± 18.55 g/L，治疗后:126.90 ± 16.54 g/L，P = 0.837)、血小板(治疗前:292.50 ± 78.51×109/L，治疗后:278.03 ± 98.54×109/L，P = 0.459)、血清 ALT(治疗前:32.39 ± 39.90 U/L、治疗后: 51.29 ± 93.90 U/L，P = 0.630)、AST(治疗前:36.52 ± 30.52 U/L，治疗后:41.07 ± 52.17 U/L，P = 0.925)、肌酐水平(治疗前:55.56 ± 15.10 umol/L，治疗后: 53.65 ± 12.53 umol/L，P = 0.645)没有显著变化。在肝、脾、肠、肾和膀胱中观
 察到 177Lu-AB-3PRGD2 的正常生理摄取。177Lu-AB-3PRGD2 显示出低的脑摄取。 膀胱的平均滞留时间最高(8.45 h)，其次是肝脏(3.96 h)，心脏(2.06 h)，和 红骨髓(2.03 h)。177Lu-AB-3PRGD2 在血液中的半减期估计约为 2.85 ± 2.17 小 时。全身有效剂量为 0.251 ± 0.047mSv/MBq。线性回归分析显示 68Ga-DOTA- 3PRGD2 PET 主要器官的 SUVmean 和 177Lu-AB-3PRGD2 SPECT 在不同时间点 的平均计数呈高度正相关，其中与 24 小时的 177Lu-AB-3PRGD2 SPECT 平均计 数相关性最高(3 小时 R = 0.830，P < 0.001;24 小时 R = 0.840，P < 0.001;48 小时 R = 0.790，P < 0.001;72 小时 R = 0.760，P < 0.001;96 小时 P = 0.760，P < 0.001;120 小时 R = 0.730，P < 0.001;168 小时 R = 0.700，P < 0.001)。68Ga- DOTA-3PRGD2 主要器官和肿瘤病变的 SUVmax 和 SUVmean 与 177Lu-AB- 3PRGD2 的吸收剂量相关(主要器官 SUVmax:R = 0.360，P < 0.001，SUVmean: R = 0.340，P < 0.001;肿瘤病变 SUVmax:R = 0.780，P < 0.001，SUVmean:R = 0.790，P < 0.001)。

研究结论:研究表明，177Lu-AB-3PRGD2 在治疗整合素 αvβ3 阳性肿瘤方面具有 良好的安全性和潜在的治疗效果，68Ga-DOTA-3PRGD2 PET/CT 可为选择放射性 核素治疗的患者提供证据。

 研究内容三 68Ga-NOTA-PRGD2 和 68Ga-pentixafor PET/CT 在颈

动脉斑块中的应用与比较
研究目的:整合素 αvβ3 在新生血管和活化的巨噬细胞中高表达，趋化因子受体 CXCR4 在巨噬细胞及白细胞等炎症细胞中表达上调，本研究的目的是评估 68Ga- NOTA-PRGD2 PET/CT 在颈动脉斑块成像中的表现，并与 68Ga-pentixafor PET/CT 比较，探索整合素 αvβ3 显像和趋化因子受体 CXCR4 显像在颈动脉斑块中的诊断 价值与优势，为疾病的诊断和治疗提供更多更精确的科学依据。 研究方法:本研究是一项前瞻性研究，共招募了 33 名准备进行颈动脉内膜剥脱 术或支架植入术的颈动脉斑块患者进行手术前的检查(27 名男性，6 名女性;年 龄:47 - 82 岁，平均值±标准差:64 ± 8 岁)，在获得所有患者的知情同意后， 对 29 名患者进行了 68Ga-NOTA-PRGD2 PET/CT 显像，9 名患者进行了 68Ga- pentixafor PET/CT 显像，其中 5 名患者同时进行了 68Ga-NOTA-PRGD2 和 68Ga- pentixafor PET/CT 显像。视觉分析所有 PET 图像是否存在局灶性放射性示踪剂 摄取，并勾画感兴趣区体积(volumes of interest, VOI)，测定患侧颈动脉病变处、 相应的对侧颈动脉、患侧颈静脉和对侧颈静脉的 SUVmean。平均靶/背景比值 ( target-to-background ratio, TBR ) 定 义 为 颈 动 脉 SUVmean/ 同 侧 颈 静 脉 SUVmean。使用 SPSS 软件进行计算。所有数据均以平均值±标准差表示。所有 统计学检验均为双侧，P < 0.05 为具有统计显著性。
研究结果:共入组了 33 名准备进行手术的颈动脉斑块患者，入组的男性占多数 (男女比为 27:6)，其中 65 及 65 岁以上的患者占到了 48.5%(16/33)，75.8% 的患者有吸烟史，24.2%的患者有家族史。29 名患者进行了 68Ga-NOTA-PRGD2 PET/CT 检查，其中有 3 名患者为双侧颈动脉斑块，其余 26 名患者为单侧颈动脉 斑块。颈动脉斑块病变的 SUVmean 和 TBRmean 比正常动脉的 SUVmean 和 TBRmean(颈动脉斑块病变 vs 正常动脉:SUVmean，1.017 ± 0.286 vs 0.982 ± 0.299，P = 0.676;TBRmean，1.361 ± 0.247 vs 1.211 ± 0.154，P = 0.010)。大于 等于 65 岁的患者与小于 65 岁的患者、吸烟的患者与不吸烟的患者和有家族史的 患者与没有家族史的患者之间的颈动脉斑块病变的 SUVmean 和 TBRmean 没有 统计学差异。68Ga-NOTA-PRGD2 PET/CT 的 SUVmean 与颈动脉斑块病变关系的 ROC 曲线下面积为 0.566，SUVmean 为 0.973 是颈动脉斑块病变的最佳阈值， TBRmean 与颈动脉斑块病变关系的 ROC 曲线下面积为 0.667，TBRmean 为 1.291 是颈动脉斑块病变的最佳阈值。9 名患者进行了 68Ga-pentixafor PET/CT 检查，所有患者均为单侧颈动脉斑块。颈动脉斑块病变的 SUVmean 和 TBRmean 比正常 动脉的 SUVmean 和 TBRmean 高(颈动脉斑块病变 vs 正常动脉:SUVmean， 1.601 ± 0.278 vs 1.327 ± 0.192，P = 0.027;TBRmean，1.599 ± 0.536 vs 1.273 ± 0.251，P = 0.118)。68Ga-pentixafor PET/CT 的 SUVmean 与颈动脉斑块病变关系 的 ROC 曲线下面积为 0.790，SUVmean 为 1.400 是颈动脉斑块病变的最佳阈值， TBRmean 与颈动脉斑块病变关系的 ROC 曲线下面积为 0.728，TBRmean 为 1.423 是颈动脉斑块病变的最佳阈值。在 5 名同时进行 68Ga-NOTA-PRGD2 和 68Ga- pentixafor PET/CT 检查的患者中，颈动脉斑块病变的 68Ga-pentixafor 的 SUVmean 和 TBRmean 高于 68Ga-NOTA-PRGD2 (SUVmean 比:1.563 ± 0.331 vs 0.852 ± 0.178;TBRmean 比:1.757 ± 0.695 vs 1.333 ± 0.243)。68Ga-NOTA-PRGD2 和 68Ga-pentixafor PET/CT 之间的 SUVmean 有统计学差异(P = 0.001)，而 TBRmean 没有统计学差异(P=0.206)。68Ga-NOTA-PRGD2 和 68Ga-pentixaforPET/CT上 颈动脉斑块病变的 SUVmean显著正相关(r=0.900，P=0.037)，而TBRmean 没有显著的相关性(r = 0.800，P = 0.104)。

研究结论: 68Ga-NOTA-PRGD2 和 68Ga-Pentixafor PET/CT 的靶点不同，但都具 有识别和评估颈动脉斑块的应用潜力，而且两者的摄取显著正相关，尽管 68Ga- Pentixafor PET/CT 在颈动脉斑块中表现出比 68Ga-NOTA-PRGD2PET/CT 更高的 摄取。
 

Project 1
Comparison of 68Ga-DOTA-3PRGD2 and 18F-FDG PET/CT in the Detection of Adenoid Cystic Carcinoma
Purpose:ACC is a rare malignant tumor that mainly occurs in secretory glands. The purpose of this study was to explore the performance of 68Ga-DOTA-3PRGD2, a diagnostic and therapeutic integrated probe targeting integrin αvβ3 with DOTA as the chelating group, in the diagnosis of ACC, evaluate the detection capabilities and uptake characteristics of 68Ga-DOTA-3PRGD2 and 18F-FDG PET/CT in ACC, and compare the effectiveness of the two imaging agents.
Methods: In this prospective study, 30 patients (15 males, 15 females; age: 22 - 70 years old, mean ± SD: 42 ± 12 years old) with ACC were recruited. All enrolled patients underwent 68Ga-DOTA-3PRGD2 PET/CT imaging, and 18 patients underwent 18F- FDG PET/CT imaging at the same time. The time interval between the two imaging sessions did not exceed 48 hours. During this period, the patient cannot receive any treatment. The images were interpreted using visual analysis and semi-quantitative analysis, and SUVmax and SUVmean semi-quantitative analysis were used to evaluate the uptake of the lesions. Calculations were performed using SPSS software. All the data were expressed as mean ± SD. All tests were two sided, and P-value < 0.05 was considered statistically significant.
Results: All 30 patients underwent 68Ga-DOTA-3PRGD2 PET/CT examination, of which 14 (46.7%) patients had local recurrence in the head and neck, and among 18 patients underwent both 68Ga-DOTA-3PRGD2 PET/CT and 18F-FDG PET/ CT, 10 (55.6%) patients had local recurrence in the head and neck. The most common metastatic sites were the lungs, followed by bones, lymph nodes, liver, pleura and pectoralis major muscle. The SUVmax and SUVmean ranges of 68Ga-DOTA-3PRGD2 PET/CT of lesions in various locations were 1.0 - 8.0 and 0.7 - 6.8 respectively (mean ± SD: 3.71 ± 1.54 and 2.53 ± 1.80). The SUVmax and SUVmean ranges of local recurrent lesions in the head and neck were 2.5 - 5.5 and 1.3 - 3.4 respectively (mean ± SD: 3.77 ± 0.90 and 2.30 ± 0.66). The ranges of SUVmax and SUVmean of lung metastases were 1.0 - 8.0 and 0.7 - 6.8 respectively (mean ± SD: 3.34 ± 1.96 and 2.23 ± 1.82), the ranges of SUVmax and SUVmean of liver metastases were 3.2 - 5.4 and 2 - 3.8 respectively (mean ± SD: 4.03 ± 1.19 and 2.63 ± 1.01), the SUVmax and SUVmean ranges of bone metastases ranges were 2.2 - 7.0 and 1.2 - 5.3 respectively (mean ± SD: 4.10 ± 1.39 and 3.20 ± 2.57). The ranges of SUVmax and SUVmean of lymph node metastases were 1.8 - 5.5 and 0.9 - 4.0 respectively (mean ± SD: 3.17 ± 1.24 and 1.90 ± 1.04), the ranges of SUVmax and SUVmean of pleural metastases were 2.1 - 7.0 and 1.2 - 5.7 respectively (mean ± SD: 4.60 ± 2.45 and 3.40 ± 2.25), the SUVmax and SUVmean of pectoralis major metastasis was 2.60 and 1.60 respectively. The numbers of positive lesions in various parts of the total body, lung metastases, and bone metastases detected by 18F-FDG PET/CT were significantly higher than that detected by 68Ga-DOTA-3PRGD2 PET/CT (total body lesions: 1491 vs 770, P < 0.001; lung metastases: 771 vs 564, P = 0.008; bone metastases: 341 vs 105, P = 0.036). The uptake of 18F-FDG in the lesions of wholebody was significantly higher than that of 68Ga-DOTA-3PRGD2 (SUVmax: 8.28 ± 5.45 vs 3.90 ± 1.62, P < 0.001; SUVmean: 5.80 ± 4.65 vs 2.56 ± 1.45, P < 0.001). The uptake of 18F-FDG in local recurrent lesions of head and neck, lung metastases, and bone metastases were significantly higher than that of 68Ga DOTA-3PRGD2. Although there was no statistically significant difference of 18F-FDG and 68Ga-DOTA-3PRGD2 in liver metastases and lymph node metastases. The uptake of 18F-FDG in pectoralis major muscle metastases was higher than that of 68Ga-DOTA-3PRGD2. On the contrary, the average uptake value of 68Ga-DOTA- 3PRGD2 in pleural metastases was higher than that of 18F-FDG (18F-FDG vs 68Ga- DOTA-3PRGD2 SUVmax: 3.95 ± 0.49 vs 4.55 ± 3.46; SUVmean: 2.05 ± 0.35 vs 3.45 ± 3.18). Correlation analysis results showed that there was a positive correlation of SUVmax (r = 0.506, P < 0.001) and SUVmean value (r = 0.539, P < 0.001) for tumors between 68Ga-DOTA-3PRGD2 PET/CT and 18F-FDG PET/CT.

Conclusion: The study was the first clinical translation of a novel molecular probe 68Ga-DOTA-3PRGD2 and the first application in the diagnosis of ACC. 18F-FDG PET/CT and 68Ga-DOTA-3PRGD2 PET/CT are both promising imaging methods for detecting ACC. 68Ga-DOTA-3PRGD2 PET/CT can provide complementary information for 18F-FDG PET/CT in specific clinical situations, and has application value in identifying systemic tumor lesions, evaluating tumor development trends and potential therapeutic targets.

 Project 2

First-In-Human Safety, Pharmacokinetics, and Dosimetry Study of 177Lu-labeled AB-3PRGD2 Targeted Therapy in Patients with Advanced Integrin αvβ3-positive Tumors
Purpose:Integrin αvβ3 is significantly overexpressed in neovasculature and various tumor cells. This study aimed to evaluate the safety, pharmacokinetics and dosimetry of a novel radiopharmaceutical, 177Lu-AB-3PRGD2, targeting integrin αvβ3. Methods: In this single-center prospective study, 10 patients with diverse malignancies (3 men, 7 women; age: 23 - 70 years, mean ± SD: 45 ± 16; BMI: 13.40 - 29.30 kg/m2, mean ± SD 20.79 ± 5.13 kg/m2; 8 adenoid cystic carcinoma, 1 cholangiocarcinoma, 1 uterine leiomyosarcoma) were recruited for treatment with 177Lu-AB-3PRGD2 (1565.84 ± 78.15 MBq, 42.32 ± 2.11 mCi), following IRB approval and informed consent from patients. All patients underwent 68Ga-DOTA-3PRGD2 PET/CT and 18F- FDG PET/CT examinations within two weeks before 177Lu-AB-3PRGD2 treatment, the time interval between 68Ga-DOTA-3PRGD2 and 18F-FDG PET/CT examinations was within 48 hours. 177Lu-AB-3PRGD2 (1565.84 ± 78.15 MBq, 42.32 ± 2.11 mCi) was administered for treatment. All patients underwent whole-body planar and SPECT/CT scans at 3, 24, 48, 72, 96, 120, and 168 h after injection. Venous blood samples were collected for radioactivity measurements at 3, 24, 48, 72, 96, 120, and 168 h after treatment. During this period, Clinical data and laboratory examinations including patients' subjective health complaints, routine blood tests, and hepatic and renal function tests before treatment and every two weeks after treatment were collected, and adverse events were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE V5.0). Repeat 68Ga-DOTA-3PRGD2 and 18F-FDG PET/CT scans 6 to 8 weeks after treatment for efficacy evaluation. The Hermes software was used to derive absorbed doses of organs，whole-body effective dose，and residence time. Calculations were performed using SPSS software. All the data were expressed as mean ± SD. All tests were two sided, and a P-value < 0.05 was considered statistically significant.
Results: The administration of 177Lu-AB-3PRGD2 was safe and well-tolerated with no significant acute adverse events or grade 4/5 toxicity. Adverse effects were noted in 3 patients, including transaminase elevations and hemoglobinopenia. Laboratory examinations showed no significant changes in WBC (6.37 ± 1.89 × 109/L before treatment, 5.92 ± 1.69 × 109 g/L after treatment, P = 0.495), HB (126.60 ± 18.55 g/L before treatment, 126.90 ± 16.54 g/L after treatment, P = 0.837), PLT (292.50 ± 78.51 × 109/L before treatment, 278.03 ± 98.54 × 109/L after treatment, P = 0.459), ALT (32.39 ± 39.90 U/L before treatment, 51.29 ± 93.90 U/L after treatment, P = 0.630), AST (36.52 ± 30.52 U/L before treatment, 41.07 ± 52.17 U/L after treatment, P = 0.925), Cr(55.56 ± 15.10 umol/L before treatment, 53.65 ± 12.53 umol/L after treatment, P = 0.645) before and after treatment. Normal physiological uptake of 177Lu- AB-3PRGD2 was observed in the liver, spleen, intestines, kidneys and bladder. 177Lu- AB-3PRGD2 showed low brain uptake. The average residence time of the bladder was the highest (8.45 h), followed by the liver (3.96 h), heart (2.06 h), and red bone marrow (2.03 h). The estimated half-life of 177Lu-AB-3PRGD2 in the blood was approximately 2.85 ± 2.17 hours. The total-body effective doses were 0.251 ± 0.047 mSv/MBq. Linear regression analysis showed SUVmean of major organs in 68Ga-DOTA-3PRGD2 PET and 177Lu-AB-3PRGD2 Counts_mean in SPECT/CT showed a high positive correlation at different time points, and it was found that the 68Ga-DOTA-3PRGD2 PET SUVmean had the highest correlation with 177Lu-AB-3PRGD2 SPECT Counts_mean at 24h (R = 0.830 at 3 h, P < 0.001; R = 0.840 at 24 h, P < 0.001; R = 0.790 at 48 h, P < 0.001; R = 0.760 at 72 h, P < 0.001; R = 0.760 at 96 h, P < 0.001; R = 0.730 at 120 h, P < 0.001; R = 0.700 at 168 h, P < 0.001). The SUVmax and SUVmean of major organs and tumor lesions in 68Ga-DOTA-3PRGD2 were correlated with the absorbed doses in 177Lu-AB- 3PRGD2(major organs:R = 0.360 for SUVmax, P < 0.001, R = 0.340 for SUVmean, P < 0.001; tumor lesions: R = 0.780 for SUVmax, P < 0.001, R = 0.790 for SUVmean, P < 0.001).

Conclusion: The study suggests that 177Lu-AB-3PRGD2 has good safety and potential therapeutic effects in managing integrin αvβ3 positive tumors，and 68Ga-DOTA- 3PRGD2 PET may provide evidence for the selection of patients for radionuclide therapy.

 Project 3

Application and comparison of 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT in carotid artery plaque
Purpose : Integrin αvβ3 is highly expressed in neovascularization and activated macrophages, and chemokine receptor CXCR4 is upregulated in inflammatory cells such as macrophages and leukocytes. The purpose of this study was to evaluate the performance of 68Ga-NOTA-PRGD2 PET/CT in carotid artery plaques imaging and compare it with 68Ga-pentixafor PET/CT to explore the diagnostic value and effectiveness of integrin αvβ3 imaging and chemokine receptor CXCR4 imaging in carotid artery plaques, which may provide more accurate scientific basis for the diagnosis and treatment of the disease.
Methods: This study was a prospective study, and a total of 33 patients with carotid artery plaques who were preparing for carotid endarterectomy or stenting (27 males and 6 females; age: 47-82 years, mean ± SD: 64 ± 8 years) were recruited. After obtaining informed consent from all patients, 68Ga-NOTA-PRGD2 PET/CT imaging was performed in 29 patients, 68Ga-pentixafor PET/CT imaging was performed in 9 patients. Among them, 5 patients underwent 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT imaging simultaneously. All PET images were visually analyzed for the presence of focal radioactive uptake, and delineated with the volumes of interest (VOI) to measure the mean standardized uptake value (SUVmean) of the affected carotid artery plaque lesion, the corresponding contralateral carotid artery, the ipsilateral jugular vein, and contralateral jugular vein. The target-to-background ratio (TBR) was defined as SUVmean of carotid artery/SUVmean of ipsilateral jugular vein. Calculations were performed using SPSS software. All the data were expressed as mean ± SD. All tests were two sided, and a P-value < 0.05 was considered statistically significant.
Results: 33 patients with carotid artery plaques who were preparing for surgery were recruited. The majority of patients was males (male:female, 27:6). Among them, 48.5% (16/33) were patients aged 65 and above, 75.8% had a history of smoking, and 24.2% had a family history. 29 patients underwent 68Ga-NOTA-PRGD2 PET/CT examination, of which 3 patients had bilateral carotid artery plaques and the remaining 26 patients had unilateral carotid artery plaques. The SUVmean and TBRmean of carotid artery plaque lesions were higher than those of normal arteries (SUVmean, 1.017 ± 0.286 vs 0.982 ± 0.299, P = 0.676; TBRmean, 1.361 ± 0.247 vs 1.211 ± 0.154, P = 0.010). There were no statistically significant differences in SUVmean and TBRmean of carotid artery plaque lesions between patients aged ≥ 65 years and patients < 65 years old, smokers and non-smokers, and patients with a family history and patients without a family history. The area under the ROC curve for the relationship between SUVmean and carotid artery plaque lesions in 68Ga-NOTA-PRGD2 PET/CT was 0.566, and SUVmean of 0.973 was the optimal threshold for carotid artery plaque lesions. The area under the ROC curve for the relationship between TBRmean and carotid artery plaque lesions in 68Ga-NOTA-PRGD2 PET/CT was 0.667, and TBRmean of 1.291 was the optimal threshold for carotid artery plaque lesions. 9 patients underwent 68Ga- pentixafor PET/CT examination, and all patients had unilateral carotid artery plaques. The SUVmean and TBRmean of carotid artery plaque lesions were higher than those of normal arteries (SUVmean, 1.601 ± 0.278 vs 1.327 ± 0.192, P = 0.027; TBRmean, 1.599 ± 0.536 vs 1.273 ± 0.251, P = 0.118). The area under the ROC curve for the relationship between SUVmean and carotid artery plaque lesions in 68Ga-pentixafor PET/CT was 0.790, and SUVmean of 1.400, was the optimal threshold for carotid artery plaque lesions, The area under the ROC curve for the relationship between TBRmean and carotid artery plaque lesions in 68Ga-pentixafor PET/CT was 0.728, and TBRmean of 1.423 was the optimal threshold for carotid artery plaque lesions. Among 5 patients who underwent both 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT examinations simultaneously, the SUVmean and TBRmean of carotid artery plaque lesions in 68Ga- pentixafor PET/CT were higher than those in 68Ga-NOTA-PRGD2 (SUVmean: 1.563 ± 0.331 vs 0.852 ± 0.178; TBRmean: 1.757 ± 0.695 vs 1.333 ± 0.243)，and there was a statistically significant difference in SUVmean between 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT (P = 0.001), while TBRmean had no statistically significant difference (P = 0.206). There was a significantly positive correlation of SUVmean for carotid artery plaque lesions between 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT(r = 0.900, P = 0.037), while TBRmean between them had no significant correlation (r = 0.800, P = 0.104).

Conclusion: 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT have different targets, but they both have the potential for identifying and evaluating carotid plaques. Moreover, the uptakes of 68Ga-NOTA-PRGD2 and 68Ga-pentixafor PET/CT were significantly positively correlated, although 68Ga-pentixafor PET/CT showed higher uptake of carotid artery plaques compared to 68Ga-NOTA-PRGD2 PET/CT.