3'-deoxy-3'-[18F]fluorothymidine positron emission tomography for response assessment in soft tissue sarcoma: a pilot study to correlate imaging findings with tissue thymidine kinase 1 and Ki-67 activity and histopathologic response.
BACKGROUND
This study sought to determine whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging allows assessment of tumor viability and proliferation in patients with soft tissue sarcomas who are treated with neoadjuvant therapy.


METHODS
Twenty patients with biopsy-proven, resectable, high-grade soft tissue sarcoma underwent [(18)F]FLT PET/CT imaging before and after neoadjuvant therapy. Histologic subtypes included sarcomas not otherwise specified (n = 5), malignant peripheral nerve sheath tumors (n = 3), gastrointestinal stromal tumors (n = 3), leiomyosarcomas (n = 3), angiosarcomas (n = 2), and others (n = 4). Changes in [(18)F]FLT peak standardized uptake value (SUVpeak) were correlated with percent necrosis in excised tissue, whereas posttreatment [(18)F]FLT tumor uptake was correlated with thymidine kinase 1 (TK1) expression and Ki-67 staining indices in excised tumor tissue.


RESULTS
Tumor FLT SUVpeak averaged 7.1 ± 3.7 g/mL (range, 1.9-16.1 g/mL) at baseline and decreased significantly to 2.7 ± 1.6 g/mL (range, 0.8-6.0 g/mL) at follow-up (P < .001); however, marked reductions in SUV were not specific for histopathological response. The posttreatment SUVpeak did not correlate with TK1 (P = .27) or Ki-67 expression (P = .21).


CONCLUSIONS
Marked reductions in [(18)F]FLT tumor uptake in response to neoadjuvant treatment were observed in most patients with sarcoma. However, these reductions were not specific for histopathologic response to neoadjuvant therapy. Furthermore, posttreatment [(18)F]FLT tumor uptake was unrelated to tumor proliferation by Ki-67 and TK1 staining. These results question the value of [(18)F]FLT PET imaging for treatment response assessments in patients with soft tissue sarcoma.
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095-1782, USA.
Matthias R
MR
Benz
Johannes
J
Czernin
Martin S
MS
Allen-Auerbach
Sarah M
SM
Dry
Piriya
P
Sutthiruangwong
Claudio
C
Spick
Caius
C
Radu
Wolfgang A
WA
Weber
William D
WD
Tap
Fritz C
FC
Eilber
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D020360:Neoadjuvant Therapy; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012509:Sarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D013937:Thymidine Kinase / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D013937:Thymidine Kinase; C092717:thymidine kinase 1