Pretreatment PET/CT imaging of angiogenesis based on 18F-RGD tracer uptake may predict antiangiogenic response

  • Li Li
  • Li Ma
  • Dongping Shang
  • Zhiguo Liu
  • Qingxi Yu
  • Suzhen Wang
  • Xuepeng Teng
  • Qiang Zhang
  • Xudong Hu
  • Wei Zhao
  • Wenhong Hou
  • Jianyue Jin
  • Feng-Ming (Spring) Kong
  • Jinming Yu
  • Shuanghu YuanEmail author
Original Article



To explore the relationship between metabolic uptake of the 18F-ALF-NOTA-PRGD2 (18F-RGD) tracer on positron emission tomography/computerized tomography (PET/CT) and the antiangiogenic effect of apatinib in patients with solid malignancies.

Materials and patients

Patients with measurable lesions scheduled for second- or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial. All patients underwent 18F-RGD PET/CT examination before the start of treatment. Standardized uptake values (SUVs) of contoured tumor lesions were computed and compared using independent sample t-tests or the Mann–Whitney U test. Receiver-operating characteristic (ROC) curve analysis was used to determine accuracy in predicting response. Survival curves were compared using the Kaplan–Meier method.


Of 38 patients who consented to study participation, 25 patients with 42 measurable lesions met the criteria for inclusion in this response assessment analysis. The median follow-up time was 3 months (range, 1–10 months), and the median progression-free survival (PFS) was 3 months (95% confidence interval, 1.04–4.96). The SUVpeak and SUVmean were significantly higher in responding tumors than in non-responding tumors (4.98 ± 2.34 vs 3.59 ± 1.44, p = 0.048; 3.71 ± 1.15 vs 2.95 ± 0.49, P = 0.036). SUVmax did not differ between responding tumors and non-responding tumors (6.58 ± 3.33 vs 4.74 ± 1.83, P = 0.078). An exploratory ROC curve analysis indicated that SUVmean [area under the ROC curve (AUC) = 0.700] was a better parameter than SUVpeak (AUC = 0.689) for predicting response. Using a threshold value of 3.82, high SUVmean at baseline was associated with improved PFS (5.0 vs. 3.4 months, log-rank P = 0.036).


18F-RGD uptake on PET/CT imaging pretreatment may predict the response to antiangiogenic therapy, with higher 18F-RGD uptake in tumors predicting a better response to apatinib therapy.


Antiangiogenic therapy Malignancies 18F-RGD PET/CT Integrin αvβ3 



The authors would like to thank Ms. Laney Weber for excellent assistance.


This study was partially funded by Shandong Key Research and Development Plan (2017CXGC1209 and 2017GSF18164) and the Outstanding Youth Natural Science Foundation of Shandong Province (JQ201423), Jinan Clinical Medicine Science and Technology Innovation Plan (201704095), NSFC81372413, National Key Research and Development Program of China (2016YFC0904700).

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.

Ethical standards

Our investigation was approved by the Shandong Cancer Hospital affiliated to Shandong University Ethical Committee. All persons gave their informed consent prior to their inclusion in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Li Li
    • 1
    • 2
  • Li Ma
    • 2
  • Dongping Shang
    • 2
  • Zhiguo Liu
    • 2
  • Qingxi Yu
    • 2
  • Suzhen Wang
    • 2
  • Xuepeng Teng
    • 2
  • Qiang Zhang
    • 3
  • Xudong Hu
    • 2
    • 4
  • Wei Zhao
    • 2
  • Wenhong Hou
    • 2
  • Jianyue Jin
    • 5
  • Feng-Ming (Spring) Kong
    • 6
  • Jinming Yu
    • 2
  • Shuanghu Yuan
    • 2
    • 4
    Email author
  1. 1.School of Medicine and Life SciencesUniversity of Jinan–Shandong Academy of Medical SciencesJinanChina
  2. 2.Department of Radiation OncologyShandong Cancer Hospital and Institute–Shandong Cancer Hospital Affiliated to Shandong UniversityJinanChina
  3. 3.Zibo Forth People’s HospitalZiboChina
  4. 4.Shandong Academy of Medical SciencesJinanChina
  5. 5.Department of Radiation OncologyIndiana University School of MedicineIndianapolisUSA
  6. 6.Department of Radiation Oncology, Simon Cancer CenterIndiana University School of MedicineIndianapolisUSA

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