Evaluation of [18F]F-DPA as a target for TSPO in head and neck cancer under normal conditions and after radiotherapy

Tuominen, Sanni; Keller, Thomas H.; Petruk, Nataliia; López-Picón, Francisco R.; Eichin, Dominik; Löyttyniemi, Eliisa; Verhassel, Alejandra; Rajander, Johan; Sandholm, Jouko; Tuomela, Johanna; Grönroos, Tove J.

doi:10.1007/s00259-020-05115-z

Cited by 8 publications

(12 citation statements)

References 37 publications

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“…We were also able to block the [ 18 F]F-DPA uptake in the inflammation site with the TSPO-selective ligand PK11195. A PK11195 dose of 1 mg reduced the [ 18 F]F-DPA uptake by 70%, which is in line with our previous studies in brain and tumors [ 12 , 15 ]. Increasing the PK11195 dose to 3 mg resulted in a complete blockade of the tracer uptake.…”

Section: Discussionsupporting

confidence: 91%

Evaluation of [18F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

et al. 2022

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Purpose Recent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ([18F]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats. Procedures Neuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post-injury. On day 7, in vivo PET imaging and ex vivo autoradiography were performed using [18F]F-DPA or [11C]PK11195. Ex vivo biodistribution and PET imaging of the removed spinal cord were carried out with [18F]F-DPA. Sham-operated and PK11195-pretreated animals were also examined. Results Mechanical allodynia was confirmed in the PSNL rats from day 3 through day 7. Ex vivo autoradiography showed a higher lesion-to-background uptake with [18F]F-DPA compared with [11C]PK11195. Ex vivo PET imaging of the removed spinal cord showed [18F]F-DPA accumulation in the inflammation site, which was immunohistochemically confirmed to coincide with microglia activation. Pretreatment with PK11195 eliminated the uptake. The SUV values of in vivo [18F]F-DPA and [11C]PK11195 PET were not significantly increased in the lesion compared with the reference region, and were fivefold higher than the values obtained from the ex vivo data. Ex vivo biodistribution revealed a twofold higher [18F]F-DPA uptake in the vertebral body compared to that seen in the bone from the skull. Conclusions [18F]F-DPA aided visualization of the spinal cord inflammation site in PSNL rats on ex vivo autoradiography and was superior to [11C]PK11195. In vivo [18F]F-DPA PET did not allow for visualization of tracer accumulation even using a high-spatial-resolution PET scanner. The main reason for this result was due to insufficient SUVs in the spinal cord region as compared with the background noise, in addition to a spillover from the vertebral body.

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Section: Discussionsupporting

confidence: 91%

Evaluation of [18F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

et al. 2022

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“…Unfortunately, most patients received [ 18 F]FET PET later in the disease course, and dual-tracer PET before radiotherapy was not available in a large number of cases in this cohort. Intentionally, this study addressed the association of TSPO PET findings and survival in newly diagnosed glioblastoma before radiotherapy (not during or after radiotherapy, where radiation treatment-related alterations of tumoral tracer uptake may occur in TSPO PET) (24). However, serial TSPO PET imaging during radiotherapy will be of interest as a potential tool for treatment response assessment.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of TSPO PET Before Radiotherapy in Newly Diagnosed IDH–Wild-Type Glioblastoma

et al. 2023

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The 18-kDa translocator protein (TSPO) is gaining recognition as a relevant target in glioblastoma imaging. However, data on the potential prognostic value of TSPO PET imaging in glioblastoma are lacking. Therefore, we investigated the association of TSPO PET imaging results with survival outcome in a homogeneous cohort of glioblastoma patients. Methods: Patients were included who had newly diagnosed, histologically confirmed isocitrate dehydrogenase (IDH)-wild-type glioblastoma with available TSPO PET before either normofractionated radiotherapy combined with temozolomide or hypofractionated radiotherapy. SUV max on TSPO PET, TSPO binding affinity status, tumor volumes on MRI, and further clinical data, such as O 6 -alkylguanine DNA methyltransferase (MGMT) and telomerase reverse transcriptase (TERT) gene promoter mutation status, were correlated with patient survival. Results: Forty-five patients (median age, 63.3 y) were included. Median SUV max was 2.2 (range, 1.0-4.7). A TSPO PET signal was associated with survival: High uptake intensity (SUV max . 2.2) was related to significantly shorter overall survival (OS; 8.3 vs. 17.8 mo, P 5 0.037). Besides SUV max , prognostic factors for OS were age (P 5 0.046), MGMT promoter methylation status (P 5 0.032), and T2-weighted MRI volume (P 5 0.031). In the multivariate survival analysis, SUV max in TSPO PET remained an independent prognostic factor for OS (P 5 0.023), with a hazard ratio of 2.212 (95% CI, for death in cases with a high TSPO PET signal (SUV max . 2.2). Conclusion: A high TSPO PET signal before radiotherapy is associated with significantly shorter survival in patients with newly diagnosed IDH-wild-type glioblastoma. TSPO PET seems to add prognostic insights beyond established clinical parameters and might serve as an informative tool as clinicians make survival predictions for patients with glioblastoma.

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“…Sites of irritation and inflammation are known to be where a variety of cancer types emerge, and the progression is known to rely on macrophage infiltration . Two tracers that have emerged as PET TSPO imaging agents are [ 11 C]PBR28, which has shown promise in tracking the accumulation and depletion of macrophages and [ 18 F]F-DPA-714, which was used to assess the effect of radiotherapy on TAMs. , A key limitation of targeting TSPO is that its presence in a variety of cell types leads to providing less selective information regarding TAMs. Utilizing CD206 as a target addresses the limitations of [ 18 F]FDG- and TSPO-targeted tracers in that it is more specific and selective to macrophages …”

Section: Discussionmentioning

confidence: 99%

Evaluation of a CD206-Targeted Peptide for PET Imaging of Macrophages in Syngeneic Mouse Models of Cancer

et al. 2023

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Tumor-associated macrophages (TAMs) are large phagocytic cells that play numerous roles in cancer biology and are an important component of the relationship between immune system response and tumor progression. The peptide, RP832c, targets the Mannose Receptor (CD206) expressed on M2-like macrophages and is cross-reactive to both human and murine CD206. Additionally, it exhibits therapeutic properties through its ability to shift the population of TAMs from an M2-like (protumor) toward an M1-like phenotype (antitumor) and has demonstrated promise in inhibiting tumor resistance in PD-L1 unresponsive melanoma murine models. In addition, it has shown inhibition in bleomycininduced pulmonary fibrosis through interactions with CD206 macrophages. 1,2 Our work aims to develop a novel CD206 positron emission tomography (PET) imaging probe based on RP832c (K d = 5.64 μM) as a direct, noninvasive method for the assessment of TAMs in mouse models of cancer. We adapted RP832c to incorporate the chelator DOTA to allow for radiolabeling with the PET isotope 68 Ga (t 1/2 = 68 min; ß + = 89%). In vitro stability studies were conducted in mouse serum up to 3 h. The in vitro binding characteristics of [ 68 Ga]RP832c to CD206 were determined by a protein plate binding assay and Surface Plasmon Resonance (SPR). PET imaging and biodistribution studies were conducted in syngeneic tumor models. Stability studies in mouse serum demonstrated that 68 Ga remained complexed up to 3 h (less than 1% free 68 Ga). Binding affinity studies demonstrated high binding of [ 68 Ga]RP832c to mouse CD206 protein and that the binding of the tracer was able to be blocked significantly when incubated with a blocking solution of native RP832c. PET imaging and biodistribution studies in syngeneic tumor models demonstrated uptake in tumor and CD206 expressing organs of [ 68 Ga]RP832c. A significant correlation was found between the percentage of CD206 present in each tumor imaged with [ 68 Ga]RP832c and PET imaging mean standardized uptake values in a CT26 mouse model of cancer. The data shows that [ 68 Ga]RP832c represents a promising candidate for macrophage imaging in cancer and other diseases.

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Evaluation of [18F]F-DPA as a target for TSPO in head and neck cancer under normal conditions and after radiotherapy

Cited by 8 publications

References 37 publications

Evaluation of [18F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

Evaluation of [18F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

Prognostic Value of TSPO PET Before Radiotherapy in Newly Diagnosed IDH–Wild-Type Glioblastoma

Evaluation of a CD206-Targeted Peptide for PET Imaging of Macrophages in Syngeneic Mouse Models of Cancer

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