Correlation between hybrid 18F-FDG PET/CT and apoptosis induced by neoadjuvant chemotherapy in breast cancer

Abstract

Quantitative or semi-quantitative analysis of fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) has been reported to correlate with the clinical and pathological response of tumors to preoperative treatment. This study was conceived to evaluate the correlation between hybrid 18 F-FDG PET/CT and apoptosis in breast cancer after neoadjuvant chemotherapy. Three cycles of neoadjuvant chemotherapy were given to forty-five patients with primary breast cancer proven by core needle biopsy. Hybrid PET/CT was performed before and after treatment and tumor to non-tumor radioactivity ratio (T/N) was calculated. The apoptotic index (AI) in core-cut and surgically resected samples was determined using TUNEL techniques. The mean T/N pre-and postchemotherapy was 3.23 ± 0.63 and 2.31 ± 0.49, respectively (p = 0.006), with the mean reduction rate below baseline of 31.18 ± 13.18% (range, 6.4-50.8%). The mean AI pre-and post-chemotherapy was 2.81 ± 0.76% and 17.31 ± 6.85%, respectively (p < 0.0001). The mean AI change was 14.34 ± 5.36% (range, 1.9-41.3%). A positive correlation was detected between the T/N reduction rate and AI change (r s = 0.850, p < 0.0001). At a threshold of 20% decrease from baseline in T/N, the mean AI change in the tumors with a reduction of 20% or more in T/N was 20.86 ± 4.29%, while that in the tumors with a reduction of less than 20% in T/N was 8.59 ± 2.87% (p < 0.0001). The sensitivity, specificity, positive and negative predictive values, and the accuracy of PET/CT for the prediction of clinical response were 90.9%, 83.3%, 93.8%, 76.9% and 92%, respectively. These data suggested that neoadjuvant chemotherapy may effectively induce apoptosis in breast tumors and decrease their glucose uptake. Hybrid PET/CT imaging appeared to be positively related to apoptosis level and therefore to be of value in predicting the response of breast cancer to neoadjuvant chemotherapy.

The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

“…CT, PET, and PET/CT images of primary tumor showing good response to neoadjuvant chemotherapy from day 8 to after completion of chemotherapy. Most of these studies evaluated treatment response after one cycle of chemotherapy and demonstrated encouraging results [14][15][16][17][19][20][21][22][23][24][25][26][27][28]. However, a recent study by Rousseau et al using PET/CT, done in the largest population, demonstrated that the optimal timing to evaluate treatment response is after two cycles of NACT.…”

99mTc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials

“…In a breast cancer clinical model, a decrease in 18 F-FDG uptake after neoadjuvant ChT was significantly and positively correlated with an increase in apoptotic index (i.e. a decrease of ≥20 % 18 F-FDG tumor-to-noise ratio from baseline was correlated with a mean increase in apoptotic index of 21±5 %) [61], and in a colorectal cancer clinical model, a [62]. In another clinical model of SCCHN, 18 F-FDG SUVmax and SUVmean with partial volume correction were correlated with the absolute number of apoptotic tumor cells (i.e.…”

In vivo imaging of apoptosis

“…While apoptosis is an energy requiring process it appears that short term tumor response is directly correlated with a significant decrease in FDG uptake in both animal models and humans. 85,86 The relationship between apoptosis and glucose utilization at the early stage of cancer chemotherapy is complex and may depend on several factors including; the time of imaging after initiation of therapy and the mechanism(s) of drug action. Many chemotherapeutic agents damage DNA via free radical oxidation, alkylation and ionizing radiation inducing a massive activation of PARP-1 as mentioned previously.…”