Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer.
OBJECTIVE
(4S)-4-(3-[(18)F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [(18)F]FSPG) is a new tracer to image x(C)(-) transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [(18)F]FSPG in patients relative to 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG). The correlation of [(18)F]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed.


METHODS
Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [(18)F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [(18)F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody.


RESULTS
[(18)F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [(18)F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [(18)F]FSPG detected 59 of 67 (88%) [(18)F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [(18)F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [(18)F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [(18)F]FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01).


CONCLUSIONS
[(18)F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [(18)F]FSPG PET may assess x(C)(-) transporter activity in patients with cancer.
Department of Nuclear Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Sora
S
Baek
Chang-Min
CM
Choi
Sei Hyun
SH
Ahn
Jong Won
JW
Lee
Gyungyub
G
Gong
Jin-Sook
JS
Ryu
Seung Jun
SJ
Oh
Claudia
C
Bacher-Stier
Lüder
L
Fels
Norman
N
Koglin
Christina
C
Hultsch
Christoph A
CA
Schatz
Ludger M
LM
Dinkelborg
Erik S
ES
Mittra
Sanjiv S
SS
Gambhir
Dae Hyuk
DH
Moon
D000328:Adult; D000368:Aged; D027182:Amino Acid Transport System y+ / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008875:Middle Aged; D049268:Positron-Emission Tomography
C569271:(4S)-4-(3-(18F)fluoropropyl)-L-glutamate; D027182:Amino Acid Transport System y+; D003287:Contrast Media; D005971:Glutamates; C118895:SLC7A11 protein, human