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 [ ¹⁸F] 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 [ ¹⁸F]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 [ ¹⁸F]FLT peak standardized uptake value (SUVpeak) were correlated with percent necrosis in excised tissue, whereas posttreatment [ ¹⁸F]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 [ ¹⁸F]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 [ ¹⁸F]FLT tumor uptake was unrelated to tumor proliferation by Ki-67 and TK1 staining. These results question the value of [ ¹⁸F]FLT PET imaging for treatment response assessments in patients with soft tissue sarcoma.