PET/CT with ¹⁸F-FLT: Does It Improve the Therapeutic Management of Metastatic Germ Cell Tumors?

Abstract

Because 18 F-FDG PET alone has only limited value in metastatic germ cell tumors (GCTs), we investigated the addition of 39-deoxy-39-18 F-fluorothymidine (FLT) to 18 F-FDG for early response monitoring and prediction of the histology of residual tumor masses in patients with metastatic GCT. Methods: Eleven patients with metastatic GCT were examined with both 18 F-FDG PET/CT and 18 F-FLT PET/CT before chemotherapy, after the first cycle of chemotherapy (early response), and 3 wk after completion of chemotherapy. In 1 patient with negative 18 F-FLT PET/CT results before chemotherapy, no further 18 F-FLT scanning was performed. PET images were analyzed visually and, using standardized uptake values (SUVs), semiquantitatively. The results were compared with the findings of CT and tumor marker levels and validated by histopathologic examination of resected residual masses, including Ki-67 immunostaining (7 patients), or by clinicoradiologic follow-up for at least 6 mo (4 patients). A responder was defined as a patient showing the presence of necrosis, a complete remission, or a marker-negative partial remission within a minimum progression-free interval of 6 mo. Early treatment response was judged according to the criteria of the European Organization for Research and Treatment of Cancer. Results: Before chemotherapy, reference lesions showed increased 18 F-FDG uptake (mean SUV, 8.8; range, 2.9-15.0) in all patients and moderate 18 F-FLT uptake (mean SUV, 3.7; range, 1.7-9.7) in 10 of 11 patients. After 1 cycle of chemotherapy, mean SUV decreased in responders and nonresponders by 64% and 60%, respectively, for 18 F-FDG (P 5 0.8) and by 58% and 48%, respectively, for 18 F-FLT (P 5 0.5). After the end of chemotherapy, mean SUV decreased in responders and nonresponders by 85% and 73%, respectively, for 18 F-FDG (P 5 0.1) and by 68% and 65%, respectively, for 18 F-FLT (P 5 0.8). The results of early and final PET were inconsistent in 6 of 11 patients for 18 F-FDG and in 4 of 10 patients for 18 F-FLT. Both patients with teratoma had false-negative results on both 18 F-FDG and 18 F-FLT. The sensitivity, specificity, positive predictive value, and negative predictive value for detection of viable tumor after 1 cycle of chemotherapy were 60%, 33%, 43%, and 50%, respectively, for 18 F-FDG and 60%, 80%, 75%, and 67%, respectively, for 18 F-FLT PET/CT. The respective values after the end of chemotherapy were 20%, 100%, 100%, and 60% for 18 F-FDG and 0%, 100%, 0%, and 50% for 18 F-FLT PET/CT. Conclusion: PET-negative residual masses after chemotherapy of metastatic GCT still require resection, since the low negative predictive value of 18 F-FDG PET for viable tumor cannot be improved by application of 18 F-FLT.

Monitoring Tumor Response to Therapy with 18F-FLT PET

“…In this context, Pfannenberg et al (27) report in this issue of The Journal of Nuclear Medicine the results of an important study comparing 18 F-FDG and 18 F-FLT PET for monitoring tumor response to chemotherapy in metastatic germ cell tumors (GCTs). GCTs are generally classified as seminomas or nonseminomas; each of these subtypes comprises approximately 50% of cases (28).…”

“…Pfannenberg et al (27) performed 18 F-FLT PET and 18 F-FDG PET scans on a group of 11 patients with GCT (10 nonseminomas and 1 seminoma).…”

PET Imaging of Proliferation with Pyrimidines

“…Although there was a trend toward increased 18 F-FLT uptake and Ki-67 index in malignant tissues, there has been considerable overlap and further studies will be needed to assess the feasibility of this technique in differentiating benign from malignant ovarian tissues. Clinical studies in germ cell tumors that have evaluated 18 F-FLT and 18 F-FDG to assess lesions for residual disease have shown limited benefits (60), probably more because of the lower uptake and sensitivity of 18 F-FLT in detecting tumors due to lower proliferation (61). Clinical studies are needed to assess 18 F-FLT PET applications in testicular cancers.…”

Postchemotherapy Residual Masses in Nonseminomatous Germ Cell Tumor Patients: 18F-FLT PET Is Unlikely to Identify Mature Teratoma, but Imaging of αvβ3 Integrin Expression Could

“…In a recent study comparing 39-deoxy-39-18 Ffluorothymidine ( 18 F-FLT) and 18 F-FDG for therapy monitoring in 11 nonseminomatous germ cell tumor (NSGCT) patients, Pfannenberg et al (1) reported 2 patients in whom resected residual masses contained mature teratoma and harbored a low 18 F-FLT uptake (mean standardized uptake value [SUV mean ], 1.4 and 0.8) similar to that observed in 2 patients with necrosis (SUV mean , 1.3 and 1.3).…”