Preclinical PET tracers for the evaluation of sarcomas: understanding tumor biology

Abstract

Sarcomas are rare tumors of mesenchymal origin. Sarcomas display significant histological heterogeneity, resulting in significant imaging heterogeneity. ¹⁸F-FDG PET has is increasingly used for the evaluation, staging and surveillance of patients with sarcomas. ¹⁸F-FDG PET maximum SUV has been shown to be correlated with sarcoma grade and overall survival. This has led to interest in alternative PET tracers to assess the biological characteristics of tumors and guide treatment decisions. Here we investigate novel PET/CT tracers used for the evaluation of sarcomas over the past 20 years and summarize what we have learned about sarcoma tumor biology from these studies.

Keywords: PET; amino acid PET tracers; hypoxia imaging; nucleoside PET tracers; sarcoma.

Figure 1

PRISMA diagram. Generated using the PRISMA Flow Diagram Generator by Toronto Health Economics and Technology Assessment Collaboration (http://prisma.thetacollaborative.ca/).

Figure 2

“Baseline and follow-up ¹⁸F-FLT positron emission tomography/computed tomography images are shown of 2 patients with angiosarcoma of the breast. The patient shown in (A) exhibited >95% tissue necrosis after neoadjuvant treatment and was classified as a histopathologic responder. The patient in (B) was a histopathologic nonresponder with <5% tissue necrosis after treatment. However, comparable decreases in ¹⁸F-FLT uptake of 85% and 71%, respectively, were seen. Therefore, the patient in (B) was misclassified as a metabolic responder by fluorothymidine positron emission tomography analysis. SUV_peak indicates peak standardized uptake value”. Reprinted, with permission, from reference [27].

Figure 3

(A) “¹¹C-tyrosine PET image of a sarcoma not otherwise specified with a relatively high PSR and (B) corresponding MIB-1 stained tissue section (400×) of the tumor showing a high number of proliferating cells. All dark nuclei express Ki-67 and have entered the cell cycle. (C) ¹¹C-tyrosine PET image of a malignant schwannoma with a relatively low PSR and (D) corresponding MIB-1 stained tissue section (400×) showing a low number of proliferating cells”. Reprinted, with permission, from reference [5].

Figure 4

“¹⁸F-FDG and ¹⁸F-FMISO scans (with an attenuation scan for localization) of a grade 2 osteosarcoma of the right femur. The ¹⁸F-FMISO image shows pixels with a tissue to blood ratio ≥1.2 in color. The correlation of ¹⁸F-FDG vs ¹⁸F-FMISO using pixel-by-pixel analysis was r=0.48 for the whole tumor”. Reprinted, with permission, from reference [47].