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Non-invasive Early Response Monitoring of Nanoparticle-assisted Photothermal Cancer Therapy Using 18F-FDG, 18F-FLT, and 18F-FET PET/CT Imaging.

ABSTRACT: Rationale: Since its first implementation nanoparticle-assisted photothermal cancer therapy has been studied extensively, although mainly with focus on optimal nanoparticle design. However, development of efficient treatment protocols, as well as reliable and early evaluation tools in vivo, are needed to push the therapy towards clinical translation. Positron emission tomography (PET) is a non-invasive imaging technique that is currently finding extensive use for early evaluation of cancer therapies; an approach that has become of increasing interest due to its great potential for personalized medicine. Methods: In this study, we performed PET imaging to evaluate the treatment response two days after nanoparticle-assisted photothermal cancer therapy in tumor-bearing mice. We used three different tracers; 2'-deoxy-2'-18F-fluoro-D-glucose (18F-FDG), 3'-deoxy-3'-18F-fluorothymidine (18F-FLT), and O-(2'-18F-fluoroethyl)-L-tyrosine (18F-FET) to image and measure treatment induced changes in glucose uptake, cell proliferation, and amino acid transport, respectively. After therapy, tumor growth was monitored longitudinally until endpoint was reached. Results: We found that nanoparticle-assisted photothermal therapy overall inhibited tumor growth and prolonged survival. All three PET tracers had a significant decrease in tumor uptake two days after therapy and these changes correlated with future tumor growth, with 18F-FDG having the most predictive value in this tumor model. Conclusion: This study shows that 18F-FDG, 18F-FLT, and 18F-FET are all robust markers for the treatment response of photothermal therapy, and demonstrate that PET imaging can be used for stratification and optimization of the therapy. Furthermore, having a selection of PET tracers that can reliably measure treatment response is highly valuable as the individual tracer might be excluded in certain applications where physiological processes limit their contrast to background.

SUBMITTER: Jorgensen JT

PROVIDER: S-EPMC5984283 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Non-invasive Early Response Monitoring of Nanoparticle-assisted Photothermal Cancer Therapy Using 18F-FDG, 18F-FLT, and 18F-FET PET/CT Imaging.

Jørgensen Jesper Tranekjær JT Norregaard Kamilla K Simón Martín Marina M Oddershede Lene Broeng LB Kjaer Andreas A

Nanotheranostics 20180427 3

Rationale: Since its first implementation nanoparticle-assisted photothermal cancer therapy has been studied extensively, although mainly with focus on optimal nanoparticle design. However, development of efficient treatment protocols, as well as reliable and early evaluation tools in vivo, are needed to push the therapy towards clinical translation. Positron emission tomography (PET) is a non-invasive imaging technique that is currently finding extensive use for early evaluation o ...[more]

PMID: 29868345

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Project description:BACKGROUND:Despite the significant upgrading in recent years of the role of 18F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[18F]fluorothymidine (18F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18F-FDG PET/CT. RESULTS:Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18F-FDG PET/CT and 18F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18F-FDG PET/CT demonstrated focal, 18F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18F-FLT PET/CT showed focal, 18F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18F-FDG avid, focal, MM-indicative lesions were detected with 18F-FDG PET/CT, while 17 18F-FLT avid, focal, MM-indicative lesions were detected with 18F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18F-FDG PET/CT than for 18F-FLT PET/CT. A common finding was a mismatch of focally increased 18F-FDG uptake and reduced 18F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUVmean and SUVmax were significantly higher for 18F-FLT than for 18F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers. CONCLUSIONS:Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that 18F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

Dataset Information

Non-invasive Early Response Monitoring of Nanoparticle-assisted Photothermal Cancer Therapy Using 18F-FDG, 18F-FLT, and 18F-FET PET/CT Imaging.

Publications

Non-invasive Early Response Monitoring of Nanoparticle-assisted Photothermal Cancer Therapy Using <sup>18</sup>F-FDG, <sup>18</sup>F-FLT, and <sup>18</sup>F-FET PET/CT Imaging.

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