(99m)Tc-3P-RGD2 SPECT to monitor early response to bevacizumab therapy in patients with advanced non-small cell lung cancer

Int J Clin Exp Pathol. 2015 Dec 1;8(12):16064-72. eCollection 2015.

Abstract

The present study assessed the predictive value of (99m)Tc-3(poly-(ethylene glycol), PEG) 4-arginine-glycine-aspartic ((99m)Tc-3P-RGD2) single photon emission computed tomography (SPECT) for the early identification of response to antiangiogenic treatment with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC treated with bevacizumab were prospectively studied with (99m)Tc-3P-RGD2 SPECT before and after 2 weeks from start of treatment. The tumor response was evaluated with RECIST criteria and related to observed change in the tumor to non-tumor (T/N) ratio for the largest known lesion. Receiver operating characteristic (ROC) curve analysis was used to determine T/N ratio changes with regard to predicting response to bevacizumab therapy. Change in T/N ratio was also related to progression-free survival (PFS) and overall survival (OS). Twenty-six patients were included, and 23 were finally assessable for metabolic response evaluation with (99m)Tc-3P-RGD2 SPECT. The cut-off value of T/N ratio change defined by ROC analysis was 24.4%. The sensitivity, specificity, and negative predictive value of (99m)Tc-3P-RGD2 SPECT for predicting tumor response were 81.8%, 91.7%, and 84.6%, respectively. Using the cut-off value defined by ROC analysis on (99m)Tc-3P-RGD2 SPECT, metabolic non-progressive disease patients (mNP) showed prolonged PFS (5.6 months versus 3.4 months; P < 0.001) and OS (17.1 months versus 8.6 months; P < 0.001) than metabolic progressive disease patients (mP). (99m)Tc-3P-RGD2 SPECT scan is a promising test to predict tumor response in patients with advanced non-small cell lung cancer early in the course of bevacizumab therapy.

Keywords: 99mTc-3P-RGD2; SPECT; bevacizumab; non-small cell lung cancer; response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Area Under Curve
  • Bevacizumab / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organotechnetium Compounds / administration & dosage*
  • Peptides, Cyclic / administration & dosage*
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Radiopharmaceuticals / administration & dosage*
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon / methods*
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Organotechnetium Compounds
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • technetium 99m (HYNIC-3PRGD(2))(tricine)(TPPTS)
  • Bevacizumab