An exploratory study on 99mTc-RGD-BBN peptide scintimammography in the assessment of breast malignant lesions compared to 99mTc-3P4-RGD2

PLoS One. 2015 Apr 7;10(4):e0123401. doi: 10.1371/journal.pone.0123401. eCollection 2015.

Abstract

Purpose: This study aimed to explore the diagnostic performance of single photon emission computed tomography / computerized tomography (SPECT/CT) using a new radiotracer 99mTc-RGD-BBN for breast malignant tumor compared with 99mTc-3P4-RGD2.

Methods: 6 female patients with breast malignant tumors diagnosed by fine needle aspiration cytology biopsy (FNAB) who were scheduled to undergo surgery were included in the study. 99mTc-3P4-RGD2 and 99mTc-RGD-BBN were performed with single photon emission computed tomography (SPECT) at 1 hour after intravenous injection of 299 ± 30 MBq and 293 ± 32 MBq of radiotracers respectively at separate day. The results were evaluated by the Tumor to non-Tumor ratios (T/NT). 99mTc-RGD-BBN and 99mTc-3P4-RGD2 SPECT/CT images were interpreted independently by 3 experienced nuclear medicine physicians using a 3-point scale system. All of the samples were analyzed immunohistochemically to evaluate the integrin αvβ3 and gastrin-releasing peptide receptor (GRPR) expression. The safety, biodistribution and radiation dosimetry of 99mTc-RGD-BBN were also evaluated in the healthy volunteers.

Results: No serious adverse events were reported in any of the patients during the study. The effective radiation dose entirely conformed to the relevant standards. A total of 6 palpable malignant lesions were detected using 99mTc-RGD-BBN SPECT/CT with clear uptake. All malignant lesions were also detected using 99mTc-3P4-RGD2 SPECT/CT. The results showed that five malignant lesions were with clear uptake and the other one with barely an uptake. 4 malignant cases were found with both αvβ3 and GRPR expression, 1 case with only GRPR positive expression (integrin αvβ3 negative) and 1 case with only integrin αvβ3 positive expression (GRPR negative).

Conclusion: 99mTc-RGD-BBN is a safe agent for detecting breast cancer. 99mTc-RGD-BBN may have the potential to make up for the deficiency of 99mTc-3P4-RGD2 in the detection of breast cancer with only GRPR positive expression (integrin αvβ3 negative). The preliminary application of 99mTc-RGD-BBN has demonstrated its powerful potential in breast cancer diagnosis and therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Mammography / methods*
  • Middle Aged
  • Oligopeptides / chemistry*
  • Organotechnetium Compounds / pharmacokinetics*
  • Radiopharmaceuticals / pharmacokinetics*
  • Tomography, Emission-Computed, Single-Photon / methods*

Substances

  • Oligopeptides
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • arginyl-glycyl-aspartic acid

Grants and funding

This research was supported by the National Natural Science Foundation of China (NSFC) projects (Grant number: 81271606), Research Fund of Science and Technology Department of Jilin Province (Grant number: 201015185, 201115088). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.