‘in Vivo Labelling Index System' in Myelomology Using an Innovative Thio-Thymidine PET/CT Combined with Amino-Acid PET/CT with Higher Visualizing Efficiency Than Conventional FDG PET/CT. - SUVmax by Thio-Thymidine PET/CT which Can Detect DNA-Synthesizing Myeloma Cell Nests in Vivo, Strongly Correlated with FISH Abnormalities in 74 Plasma Cell Dyscrasia Patients
Authors: Miwa Akiyoshi , Hagiwara Shotaro , Hirai Risen , Kubota Kazuo , Okazaki Momoko 
Published: October 2019

Abstract

Aim
FDG-PET/CT has been used in myeloma patients to evaluate tumor burden including extramedullary disease (EMD). The detection of myeloma foci by FDG PET/CT correlated with outcome and prognosis by some reports. However, some myeloma cell nests or EMD could not be detected by FDG PET/CT due to non-enhanced glucose uptake in some myeloma cases. Biologically, myeloma cells are highly protein-synthesizing cells, implying uptake of radio-labelled amino acid is enhanced. Therefore, theoretically, amino-acid PET/CT can efficiently detect myeloma cell nests. In addition, myeloma cells could show enhanced DNA synthesizing activity, especially in relapsing cases. From this point of view, we introduced new PET/CT systems to evaluate myeloma disease activity using amino-acid PET/CT and thio-thymidine PET/CT.

Patients & methods
Three modes of PET/CT included conventional FDG-PET/CT (FDG-PET), amino acid PET/CT (visualized by C11-methionine uptake, MET-PET) and an innovative thio-thymidine (visualized by sulfated C11-thio-thymidine uptake, not easily cleaved in blood, 4DST-PET). 4DST-PET is an only one PET/CT where radio-labelled material can be incorporated into cellular DNA synthesis. Seventy myeloma patient(pt)s & 4 MGUS pts were included. Forty-five myeloma pts were from our institute & 29 cases from related hospitals. Three types of PET/CT were completed in all 74 cases. G-binding studies (not CD-138 positively selected) were available in all cases, and FISH studies were available in 27 pts among our 45 pts. Temporal profile of PET findings was analyzed in 4 CRs cases.

Results
1. Distribution of pts.: 70pts except 4 MGUS pts were classified into 3 groups by Durie's PLUS staging as follows: 48 cases in PLUS stage 1 (with FDG-PET hot spot 0-4), 15 cases in stage II (FDG 5-20), and 7 cases in stage III (FDG > 20). 2. Distribution of mean hot spot numbers between FDG-PET & MET-PET: in PLUS stage I: FDG/MET = 0.45±1.1/3.22±5.33, stage II: FDG/MET = 8.54±2.6/ 15.0±11.9, stage III: FDG/MET = 34.0±19.1/46.3±22.4. Almost always, MET-PET-positivity was higher than FDG-PET positivity in all PLUS stagings I to III. 3. Upstaging : Seven cases among 48 PLUS stage I showed hot spot numbers higher than 5, implying up-staging was possible using MET-PET. 4. Correlation of 4DST-PET SUVmax in MET-PET positive area with myeloma biology; the value of SUVmax strongly correlated with the presence of FISH abnormalities including t(4;14), t(14;16), 17p-, 13 abnormalities and etc. FISH abnormalities (+) pts showed significantly higher SUVmax compared with FISH abnormalities (-) pts.(6.89 vs 0.59, p<0.0001). 5. 100% positivity of hot spots by MET-PET in CRs (FLC normal) pts. 6. In MGUS pts, 3 PETs showed negativity. 6. pathological study: Percentage of myeloma cells in bone marrow biopsied specimen from pelvic bone correlated the SUVmax in pelvic bone. Is some cases, biopsied materials of hot spots (eg. sacrum) judged by 3 PET-CT contained myeloma cell clusters.

Discussion
Through present study, MET-PET could detect more myeloma-related lesions than conventional FDG-PET. Besides, thio-thymidine PET combined with MET-PET could detect highly DNA-synthesizing myeloma nests in vivo, implying ' in vivo labelling index system' is feasible using this innovative approach. Further study might confirm the efficiency of these new PET/CT systems.

Disclosures:
No relevant conflicts of interest to declare.