title: Treatment response evaluation with18F-FDG PET/CT and18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
abstract: OBJECTIVE
  The aim of this study was to assess the combined use of the radiotracers18F-FDG and18F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).
  
  
  METHODS
  Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with18F-FDG and18F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).
  
  
  RESULTS
  An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment,18F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria,18F-FDG PET/CT-based treatment response revealed CR in 14 patients (18F-FDG PET/CT CR), PR in 11 patients (18F-FDG PET/CT PR) and progressive disease in four patients (18F-FDG PET/CT PD). In terms of18F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible,18F-NaF PET/CT depicted 56 of the 12918F-FDG positive lesions (43 %). Follow-up18F-NaF PET/CT showed persistence of 81.5 % of the baseline18F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to18F-FDG negative. Treatment response according to18F-NaF PET/CT revealed CR in one patient (18F-NaF PET/CT CR), PR in five patients (18F-NaF PET/CT PR), SD in 12 patients (18F-NaF PET/CT SD), and PD in seven patients (18F-NaF PET/CT PD). Dynamic18F-FDG and18F-NaF PET/CT studies showed that SUVaverage, SUVmax, as well as the kinetic parameters K1, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p < 0.001).
  
  
  CONCLUSIONS
  F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of18F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand,18F-NaF PET/CT does not seem to add significantly to18F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.
authors: Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69210, Heidelberg, Germany. christos_saxpe@yahoo.gr.|Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. christos_saxpe@yahoo.gr.
authors: Christos
authors: http://orcid.org/0000-0001-8739-8741
authors: C
authors: Sachpekidis
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors: J
authors: J
authors: Hillengass
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.|National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
authors: H
authors: H
authors: Goldschmidt
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors: B
authors: B
authors: Wagner
authors: Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69210, Heidelberg, Germany.|Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany.
authors: U
authors: U
authors: Haberkorn
authors: Department of Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: K
authors: K
authors: Kopka
authors: Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69210, Heidelberg, Germany.
authors: A
authors: A
authors: Dimitrakopoulou-Strauss
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000000981:diagnostic imaging* / Q000628:therapy*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012969:Sodium Fluoride; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D012969:Sodium Fluoride; D008558:Melphalan
keywords: 18F-FDG; 18F-NaF; Autologous stem cell transplantation; High-dose chemotherapy; PET/CT; Two-tissue compartment model