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3070 Background: Imaging of tumor proliferation has been studied with FLT-PET in various tumor types including NSCLC. Pemetrexed inhibits thymidylate synthase(TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). TS inhibition upregulates the thymidine salvage pathway including relocalisation of ENT1 to membrane and TK1 activation as a transient “flare” response. We hypothesise that this can be detected as an increase in FLT tumoral uptake that subsequently decreases with reduced proliferation. This study was conducted to assess FLT uptake as an early pharmacodynamics(PD) marker of pemetrexed response. Methods: This was an open-label imaging study in 21 patients with Stage 3/4 NSCLC treated with pemetrexed and platinum-based chemotherapy. Patients underwent FLT PET/CT scan at baseline and 4h after administration of pemetrexed. Platinum component of treatment was administered on the day after second FLT scan for cycle 1. Plasma for TK1 activity expression were collected before each scan time point and analysed by ELISA. Percentage change in standardized uptake value (%ΔSUV) was calculated as [SUV(PET2) – SUV(PET1)]/ SUV(PET1)*100. Treatment response calculated by RECIST 1. 1 and survival data were collected. Results: 17 patients had evaluable PET/CT scans for pemetrexed response. Median percentage difference for SUVmean and SUVmax in tumour lesions increased by 3% and 10.3% respectively. 5 patients showed homogeneous FLT flare at 4h after pemetrexed, 2 patients had decrease, 10 patients had heterogeneous FLT response (regardless of platinum doublet). There was no significant correlation between plasma TK1 activity and FLT flare. At 9 weeks, 4 patients had partial response, 9 stable disease and 4 progressive disease. Baseline and weighted average ΔSUVmax were not associated with survival. The 5 patients with FLT flare in all lesions showed a median OS of 31 months, unlike the group with heterogenous or decrease uptake(15 months). FLT uptake in bone marrow and small bowel significantly increased at 4h (t test p = 0.004, p = 0.004, respectively) indicating increased thymidine salvage activity. Early FLT uptake was not predictive for tumour RECIST response or OS. In multivariable cox regression analysis, pre-treatment TK1 activity, adjusted for performance status, smoking history and age, independently affected survival in this group (p = 0.011). Conclusions: Early FLT flare at 4h was seen in NSCLC post pemetrexed administration indicating activation of thymidine salvage pathway. Median overall survival of patients with an FLT flare response was more than twice longer than patients with mixed or no response. However, the small sample size lacked power to show statistical significance in the OS comparison. Further studies should evaluate this and the relationship to other prognostic variables in a larger cohort of patients. Clinical trial information: NCRI UK badge 9249.

3069 Background: Over-expression the human epidermal growth factor receptor-2 (HER2) is seen in 20% of breast cancers; this is an adverse prognostic factor and used to guide therapy selection. At present HER2 expression can only be determined using biopsy material using immunohistochemistry or fluorescence in situ hybridisation. Heterogeneous expression of HER2 is now being recognised as a cause of treatment resistance but is difficult to characterise. A non-invasive method for determining HER2 expression could have several advantages and help select appropriate therapy for patients. GE-226 is a novel radiolabelled GE-Affibody radioligand which binds to the HER2 receptor with high affinity at a different epitope than trastuzumab. Methods: Patients with locally advanced or metastatic breast cancer were recruited and scanned for 65 mins after iv injection of 200MBq of GE-226 (mean activity injected for each patient 202MBq (range 164-223MBq, mean radiochemical purity 94%) of radioligand, over one bed position for dynamic imaging, followed by a half-body scan. Blood sampling was used to measure metabolism of the tracer. Safety was assessed. HER2-extracellular domain (ECD) domain was measured in blood. Tumoural uptake was quantified by semi-quantitative and fquantitative parameters in HER2 positive and HER2 negative tumours. Patients had routine baseline FDG imaging. Results: Twenty patients completed the study. GE-226 scans were well tolerated. There were no serious adverse events. GE-226 was slowly metabolised into a single metabolite in the liver; 97% of parent remained at 60 minutes post injection (range 82-100). There was a significant difference in tumoural radioligand uptake between biopsy proven HER2 positive and HER2 negative tumoural patients as measured by SUVmean and SUVmax (p < 0.001). Comparing HER2 positive to HER2 negative cases, there was also a significant difference between tumour to normal tissue uptake ratios SUVmean. Heterogeneous uptake was observed in three patients, two with interlesional uptake variation and one with intralesional heterogeneity. Tumoural uptake increased over time. Normal physiological uptake in salivary glands and the thyroid gland was noted. GE-226 was able to differentiate between lymphadenopathy due to sarcoidosis and cancer in one patient and was superior to FDG which had shown widespread uptake in the benign and malignant nodes. Conclusions: [18F]GE-226 imaging is well tolerated and shows promise for imaging of HER2 positive breast cancer. Further studies with this agent are now planned. Clinical trial information: NCT03827317.

576Background: EXE-EVE significantly improved progression free survival (PFS) in patients (pts) with HR+ MBC progressing on a nonsteroidal aromatase inhibitor regardless of age, at the expenses of ...

e23140Background: The steroid sulfatase (STS) pathway is involved in oestrogen biosynthesis. Irosustat is a 1st generation, orally active, irreversible STS inhibitor. Changes in the expression of t...

635 Background: About a third of HER2-overexpressing (HER2+) breast cancer pts will develop brain metastases in the course of their disease. Drug access to normal brain and brain metastases is therefore key to prevention and treatment of cerebral metastases. To provide direct evidence of Lap drug access and evaluate whether therapeutic doses of Lap act as a substrate for efflux transporters, thereby increasing Lap concentrations, we performed positron emission tomography (PET) studies with [11C]Lap. Methods: Pts with HER2+ MBC with an ECOG of 11C]Lap before and after 8 days of oral Lap (1500 mg once daily). Arterial blood samples were performed to assess [11C]Lap radioactivity contribution in blood and plasma, and the fraction of plasma [11C] radioactivity corresponding to metabolites. Tissue time-radioactivity curves (TACs) were generated and [11C]Lap exposure (AUC; area under TAC) derived for normal brain and brain metastases. Signal dissection of the total image activity was performed to remove the contribution of blood volume to the image and the actual tissue contribution due to [11C]Lap obtained. Results: 6 pts (3 with brain metastasis) were recruited. Arterial plasma analysis revealed that [11C]Lap contributed to >80% of activity in plasma at 60 minutes. Tissue data revealed [11C]Lap signal in normal brain was low with no appreciable uptake observed when corrected for blood volume contribution. [11C]Lap uptake was higher in brain metastases compared with normal brain and appreciable, even after correction for tissue blood volume contribution. Uptake was also observed in extra-cranial normal tissue. There was no difference in [11C]Lap uptake in normal brain and metastases between treatment-naïve and post-treatment scans. Conclusions: [11C]Lap uptake in brain metastases was higher than in normal brain. [11C]Lap drug access to brain metastases might therefore indicate possible efficacy against HER2+ brain metastases. Clinical trial information: NCT01290354.

e13546 Background: The evaluation of pelvic lymph node status has important therapeutic and prognostic significance in prostate cancer. Pelvic lymphadenectomy (PL) is considered the benchmark for s...

1110 Background: Molecular imaging techniques are increasingly being used in cancer diagnosis, staging, and assessment of response to treatment. This study sought to evaluate, for the first time, [11C]choline-PET in patients with breast cancer. The potential of [11C]choline-PET for differentiating tumours from normal tissue, correlation with molecular markers, determine its normal variability range, and finally the effect of trastuzumab on [11C]choline uptake in patients with breast cancer was investigated. Methods: 21 patients with newly diagnosed and recurrent breast cancer AJCC stage II-IV were enrolled in the study, all of whom had a baseline dynamic [11C]choline-PET scan with arterial sampling. 14 patients had 2 [11C]choline-PET scans to examine reproducibility, and 7 had a scan after trastuzumab. Analysis of [11C]choline uptake was measured using SUV, Ki (irreversible retention), and IRF@60min (retention using spectral analysis). Results: Breast tumour lesions were visualised by [11C]choline PET in all patients. The difference in tumour and non-tumour uptake were significant for SUV, Ki, and IRF@60 min (Wilcoxon p < 0.0001 for all parameters). [11C]choline uptake was reproducible in breast tumour lesions (r2 = 0.945 for SUV, 0.894 for Ki, and 0.799 for IRF60). The metabolism analysis of arterial plasma samples in 19 patients showed that [11C]choline decreased rapidly post-injection such that at 60 mins the mean radioactivity in arterial plasma due to choline was 15.15 ± 2.16%.Early responses to trastuzumab were determined to be significant in 5 lesions which corresponded with 3 clinical responses. Conclusions: [11C]choline-PET is a promising imaging modality in breast cancer, and could play an important role for determining response to novel treatment strategies in vivo. No significant financial relationships to disclose.

14067 Background: In vivo imaging of avβ3 expression in tumors and tumor endothelial cells may be a useful biomarker of angiogenesis. [18F]AH11585 is a novel peptide containing an Arginine-Glycine-Aspartic Acid (RGD) motif that binds to avβ3 with high affinity designed for use in PET studies. Methods: 7 patients with metastatic breast cancer (aged 37–68 years) received intravenous injections of [18F]AH11585 and were scanned dynamically by PET over 61.5 mins. Radioactivity concentrations, derived from regions of interest placed on tumour and normal tissues, were analysed mathematically to determine the net irreversible uptake (Ki), fractional retention (FRT) and standardized uptake at 56.5min (SUV) of the radiotracer. Computed tomography (CT) was performed within 4 weeks of the scan. Results: Tumor lesions were clearly visible on PET images in 6/7 patients. In one patient with a palpable supraclavicular lymph node not visible on CT, we were unsure if a hyperintense region visible by PET was tumor. In total 18/19 tumor lesions were identified on both PET and corresponding CT images. Tumors in areas of low background were hyperintense (lung, bone, breast) whereas those in areas of high background were hypointense regions (liver). Tumors with central necrosis showed high uptake of [18F]AH11585 around the periphery only. Mathematical analysis demonstrated irreversible retention of [18F]AH11585 in tumors. [18F]AH11585-PET discriminated between non-liver lesions (n=10) and normal tissues: Ki (p=0.002), FRT (p=0.0039), SUV (p=0.002). Corresponding comparisons for liver lesions (n=8) were significant for FRT (p=0.0078) and SUV (p=0.0078) only. Conclusions: [18F]AH11585 PET is a promisng method for in vivo imaging of avβ3 integrin expression in metastatic breast cancer. No significant financial relationships to disclose.

613 Background: [11C]Choline is a novel PET radiotracer. Preclinical studies suggest that it may be promising in breast cancer. [11C]Choline has been recently evaluated as a screening agent in prostate cancer, but no studies have yet investigated its potential in breast cancer. We report a pilot study evaluating the utility and reproducibility of [11C]Choline-PET in breast cancer. Methods: Dynamic imaging was performed on an ECAT962 HR+ PET scanner for 65 min after intravenous injection with 190–369 MBq [11C]choline. Patients with locally advanced and metastatic breast cancer were eligible. All histological subtypes were included (ductal, lobular, and inflammatory). Arterial blood samples were taken continuously for 10 min, with 8 discrete samples up to 60 min to measure [11C]choline and metabolites. Tissue uptake was determined by standardised uptake value at 60 min (SUV, dose and BSA corrected) and Ki (irreversible trapping) calculated using Patlak (corrected for [11C]choline metabolites in plasma) and modified Patlak analysis (corrected for plasma + tissue metabolites). Reproduciblilty scans were performed 2–17 days later in the absence of treatment. Results: Tumour [11C]choline uptake was observed in 10 out of 11 patients (12 out of 13 distinct lesions). There was a significant difference between tumour and normal tissue (breast/lung) in [11C]choline uptake for Ki (p11C]choline was rapidly metabolised, at 60 min the mean ± S.E. plasma radioactivity due to [11C]choline was 16.4 ± 2.9%. [11C]Choline uptake was found to be reproducible for Ki (modified Patlak: r=0.93, pst scan). Tumour Patlak Ki was 13.2% > Ki calculated using modified Patlak analysis. Conclusions: [11C]Choline-PET imaging of breast cancer is promising and warrants further evaluation. Tumour [11C]Choline uptake measured by Ki and SUV is reproducible. We plan to study the relationship between choline uptake measured by PET and immunoassays of tumour samples. Functional imaging could have a vital role to determine the efficacy of target-specific agents. No significant financial relationships to disclose.

2084 Background: Current radiological methods for assessing treatment response in breast cancer provide little information on tumour biology and often require several cycles of treatment before cha...