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 SUV_max (SUV_max,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 SUV_max,avg between patients with adenocarcinoma or t-SCNC (SUV_max,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 SUV_max) 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. All patients (n =34)Confirmed adenocarcinoma histology (n = 14)Confirmed t-SCNC histology (n = 6)Osseous and soft tissue lesions
Total, n
⁶⁸Ga-citrate PET avid, n (%)483
325 (67.3)189
127 (67.2)89
62 (69.7)Osseous lesions
Total, n
⁶⁸Ga-citrate PET avid, n (%)420
313 (74.5)136
114 (83.8)89
62 (69.7)Soft tissue lesions
Total, n
⁶⁸Ga-citrate PET avid, n (%)63
12 (19.0)53
12 (22.6)0
0 (N/A)SUV_max,avg (SD)6.7 (3.8)7.3 (3.0)7.6 (6.0)