Abstract P5-01-02: Evaluation of apoptosis in breast cancer using the novel PET probe [18F]ICMT-11 in patients treated with neoadjuvant FEC chemotherapy: Initial assessment of optimum imaging time and relation to caspase-3 immunostaining

Abstract

Abstract Background: [18F]ICMT-11 is an isatin analogue which has been developed by our group as a novel PET radiotracer for studies of apoptosis in vivo. Preclinical studies have demonstrated subnanomolar affinity to caspase 3, and validated the potential for imaging apoptosis in xenograft models. A first-in-man study showed that the agent was well tolerated with acceptable dosimetry. This is the first study of this agent to measure the effect of chemotherapy on radiotracer uptake in patients. As apoptosis is a dynamic process, one of the main objectives of the study was to determine the optimal time-point for imaging post-chemotherapy and compare the results with immunohistochemistry assessments at the same time-points. The study was approved by a regional ethics committee and ARSAC. Methods: 7 patients with breast tumour lesions measuring 15mm or more, due to undergo neoadjuvant chemotherapy with FEC (5FU, Epirubicin, Cyclophosphamide) had dynamic PET scans for 66mins 30seconds following intravenous injection of [18F]ICMT-11 with a mean activity of 340.82 Mbq±20.76 and Specific Activity range of 447.014-5128.34 Gbq/µmol prior to chemotherapy and 24h-2 weeks post-chemotherapy. A breast biopsy was also obtained within a few hours of the 2nd PET scan to correlate apoptosis in the breast tissue utilising TUNEL and Caspase 3 staining by immunohistochemistry. Volumes of interest were drawn manually and analyzed using Analyze software®. Results: The scans were well tolerated in all patients. Uptake of [18F]ICMT-11 was demonstrated in all tumor lesions. The tumours studied included ER positive and PR positive, HER2 positive and triple negative patients. The first cohort patients were imaged pre-chemotherapy and 24-48h post chemotherapy. Tumour to Breast ratio (TBR) showed an increase from 1.42±0.21(pre) to 1.71±0.33 (post). Tumour to muscle ratio (TMR) was not increased, 1.52±0.30(pre) and 1.22±0.09 (post). In addition, an increase the SUV was noted in the lymph nodes of patients, at both 24 and 48h. (SUVav 0.39±0.02 (pre), 0.45±0.03 (post), and SUVmax 0.87± 0.02(pre) ,1.22±0.12 (post). The lymph nodes were however not sampled for immunohistochemistry. A further cohort of patients had the follow-up scan 2 weeks post chemotherapy, TBR and TMR were both increased in this cohort 1.50±0.22 (pre), 2.52±0.48 (post),and 1.82±0.10 (pre), 2.08±0.0.04 (post), respectively. Caspase and TUNEL labelling with immunohistochemistry also showed increased in apoptosis in the breast biopsies at 2 weeks compared to baseline in keeping with the PET data. Conclusion: These preliminary data suggest that [18F]ICMT-11 is a promising marker for chemotherapy induced apoptosis in vivo, and correlates with findings in tumor biospsies using TUNEL and immunostaining for caspase 3. Further work is underway to study a larger cohort of patients, and identify the optimal PET pharmacokinetic parameter to describe [18F]ICMT-11 uptake and retention. Citation Format: Shairoz Merchant, Eric O Aboagye, Adrian Lim, Kasia Kozlowski, Naina Patel, Jennifer Steel, Susan Cleator, Sami Shousha, Vidhya Varghese, Raoul C Coombes, Laura Kenny. Evaluation of apoptosis in breast cancer using the novel PET probe [18F]ICMT-11 in patients treated with neoadjuvant FEC chemotherapy: Initial assessment of optimum imaging time and relation to caspase-3 immunostaining [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-02.