18F-Fluorothymidine Positron Emission Tomography in Patients with Suspect Lymphoma Relapse
Authors: Broccoli Alessandro , Zanoni Lucia , Nanni Cristina , Montini Giancarlo , Stefoni Vittorio , Pellegrini Cinzia , Gandolfi Letizia , Fonti Cristina , Lodi Filippo , Cavo Michele , Fanti Stefano , Zinzani Pier Luigi 
Published: November 2019

Abstract
Introduction. A monocentric prospective study was designed to evaluate the role of F-18-fluoro-3-deoxy-3-L-fluorothymidine (FLT) PET/CT in lymphoma patients presenting with positive or equivocal F-18-deoxyglucose (FDG) PET/CT at end-treatment or follow-up evaluation.
Methods. From May 2010 to March 2015, 40 patients were enrolled in the study, all undergoing FLT PET/CT within 3 weeks from a previous positive FDG scan and, when possible, biopsy confirmation as standard of reference to define PET results (true positive-TP; true negative-TN; false positive-FP; false negative-FN). The highest lesion standardized uptake value (SUVmax) was measured with both tracers. Median age was 55 (range 20-76); 24 patients were male and 16 female. Thirty patients had non-Hodgkin lymphoma and 10 Hodgkin lymphoma (HL). At diagnosis, 8 patients had stage II, 8 stage III and 24 stage IV. Six patients were evaluated at the end of their treatment and 34 during follow-up.
Results. FDG-PET was judged positive in 36 out of 40 cases (SUVmax range 3-31; mean 10.1); 28/36 resulted also FLT positive (SUVmax range 3-16.8; mean 7.8) and 16/28 patients had the most active lesion biopsied, demonstrating 15 TP but 1 FP (cervical node, patient with a history of HL, SUVmax 6.9 and 6.8 for FDG and FLT respectively: reactive follicular hyperplasia). The remaining 12 patients could not be biopsied: however, clinical judgment and subsequent follow-up data confirmed 11 TP cases and 1 FP (reactive node). Eight FLT scans resulted inconclusive because of the low SUVmax values (range: 1.7-11.7; mean 4.8); 5 were judged as TP at biopsy (2 patients) or clinical evaluation (3 patients), whereas 3 represented reactive-inflammatory tissue. Among the 4 FDG-PET considered inconclusive (SUVmax range 4.9-8.8; mean 7.2), 3 out of 4 also resulted FLT inconclusive (SUVmax range 2.6-4.9; mean 4), but the final clinical evaluation excluded lymphoma (1 reactive cervical node, 1 nodal sarcoid-like disease, 1 aspecific pericecal finding). The remaining 1/4 resulted FLT positive (SUVmax 6.9 and 6.5 for FDG and FLT, respectively) and was clinically confirmed to be a TP case.
Conclusions. In the particular setting of residual/recurrent lymphoma, our preliminary data suggest that FLT can be complementary to FDG, although the elimination of inconclusive PET findings remains a controversial step. Further lesion-based, semi-quantitative analyses (i.e. target to background/mediastinal blood pool/liver ratio) and correlation with Ki67 proliferation index are ongoing.

Disclosures
Cavo: Janssen: Honoraria; Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria. Zinzani:Pfizer: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.