Feasibility study of gallium-68 citrate PET as a bone-tropic imaging biomarker in mCRPC.

31 Background: Transferrin receptor (TFRC) expression is controlled by the PI3K and MYC signaling pathways, which are frequently dysregulated in prostate cancer (PC). Gallium-68 citrate (68Ga-citrate) is an iron biomimetic, which can be used to image PC in a TFRC dependent fashion. We performed a single-center pilot imaging study to investigate the use of 68Ga-citrate PET in patients with metastatic castration-resistant PC (mCRPC). Methods: Following written informed consent, mCRPC patients were prospectively enrolled and underwent 68Ga-citrate PET imaging. Optional metastatic tumor biopsies were undertaken at the time of imaging. Results: 34 mCRPC patients underwent 68Ga-citrate PET imaging. The median age was 67.5 years old. Median duration of castration resistance was 17.5 months; 14.7% of patients were post-docetaxel. Median serum PSA was 35.2 ng/dL. A total of 483 lesions were detected on conventional imaging (CT, 99mTc-HDP) or 68Ga-citrate PET, including 420 osseous and 63 soft tissue (nodal and visceral) lesions (Table). 67.3% of all lesions were detected on 68Ga-citrate PET, including 74.5% of all osseous lesions but only 19.0% of all soft tissue lesions (p<0.0001). Eight (1.7%) lesions were detected on 68Ga-citrate PET imaging only. Per-lesion average SUVmax (SUVmax,avg) was 6.7. Metastatic biopsies of PET avid lesions were performed in 20 patients (59%); adenocarcinoma histology was confirmed in 14 (70%) cases, treatment-emergent small cell neuroendocrine cancer (t-SCNC) in 6 (30%). There was no significant difference in SUVmax,avg between patients with adenocarcinoma or t-SCNC (SUVmax,avg 7.3 vs 7.6, respectively; Table). Serial 68Ga-citrate PET perfomed in a patient with biopsy-confirmed t-SCNC after 2 cycles of carboplatin/cabazitaxel demonstrated an early metabolic response (28.5% decrease in average SUVmax) confirmed on subsequent conventional imaging. Conclusions: 68Ga-citrate PET detects mCRPC bone metastases in patients with biopsy-proven prostatic adenocarcinoma or t-SCNC, distinguishing it from lineage dependent agents such as PSMA tracers. Detection of an early metabolic response in the bone of a treated t-SCNC patient was observed. Further prospective studies are ongoing coupling serial Ga-citrate PET with investigational agents targeting the MYC signaling pathway. Clinical trial information: NCT02391025. [Table: see text]

Early metabolic response assessment of breast cancer liver metastases: 4-week posttreatment FDG PET predicts survival after 90Y microsphere radioembolization

Aim To evaluate the feasibility of early metabolic response assessment with 18F-FDG PET/CT in patients with breast cancer liver metastases 4 weeks after radioembolization with Yttrium-90 labeled microspheres. Methods 25 patients (mean age 58y, range 40–74) with advanced stage liver metastases of breast cancer were treated with 1.9 ± 0.4 GBq of 90Y-microspheres in the salvage setting and underwent 18F-FDG PET/CT at baseline and 4 weeks post-radioembolization. 14 patients (56 %) had an excessive hepatic tumor burden (> 50 % of total liver volume), 21 patients (84 %) had extrahepatic disease. Liver lesions with the highest SUVmax were selected as target lesions and a cut-off was set at 50 % reduction to separate responders from non-responders. The predictive impact of metabolic response on overall survival (OS) was investigated along with other prognostic factors. Results The median OS in this highly advanced metastatic cohort was 7 months (95 % CI, 5–9). All patients had a reduction in SUVmax (mean ΔSUVmax: –49 ± 26 %) at 4 weeks post-treatment. Patients with > 50 % SUVmax reduction survived longer (median OS 13 mo, 95 % CI 8–18) than the remaining patients (median OS 4 mo, 95 % CI 2–6; p = 0.001). From all investigated baseline factors including age, performance status, and presence of extra-hepatic disease, only the hepatic tumor burden had a significant impact on OS (p = 0.02). Conclusions This is the first preliminary evidence in breast cancer that early post-radioembolization molecular response assessment of treated liver metastases – as early as 4 weeks posttreatment – may predict survival. If confirmed by larger series, FDG PET/CT could be considered for early response-adapted treatment modifications.