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Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy. A major challenge in patient management is the lack of a reliable imaging tool to monitor tumor response to treatment. Tumor-associated fibrosis characterized by high type I collagen is a hallmark of PDAC, and fibrosis further increases in response to neoadjuvant chemoradiotherapy (CRT). We hypothesized that molecular positron emission tomography (PET) using a type I collagen-specific imaging probe, 68 Ga-CBP8 can detect and measure changes in tumor fibrosis in response to standard treatment in mouse models and patients with PDAC. Methods: We evaluated the specificity of 68 Ga-CBP8 PET to tumor collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in nude mouse models of human PDAC including FOLFIRNOX-sensitive (PANC-1 and PDAC6) and FOLFIRINOX-resistant (SU.86.86). Next, we demonstrated the specificity and sensitivity of 68 Ga-CBP8 to the deposited collagen in resected human PDAC and pancreas tissues. Eight male participant (49-65 y) with newly diagnosed PDAC underwent dynamic 68 Ga-CBP8 PET/MRI, and five underwent follow up 68 Ga-CBP8 PET/MRI after completing standard CRT. PET parameters were correlated with tumor collagen content and markers of response on histology. Results: 68 Ga-CBP8 showed specific binding to PDAC compared to non-binding 68 Ga-CNBP probe in two mouse models of PDAC using PET imaging and to resected human PDAC using autoradiography (P < 0.05 for all comparisons). 68 Ga-CBP8 PET showed 2-fold higher tumor signal in mouse models following FOLFIRINOX treatment in PANC-1 and PDAC6 models (P < 0.01), but no significant increase after treatment in FOLFIRINOX resistant SU.86.86 model. 68 Ga-CBP8 binding to resected human PDAC was significantly higher (P < 0.0001) in treated versus untreated tissue. PET/MRI of PDAC patients prior to CRT showed significantly higher 68 Ga-CBP8 uptake in tumor compared to pancreas (SUV mean : 2.35 ± 0.36 vs. 1.99 ± 0.25, P = 0.036, n = 8). PET tumor values significantly increased following CRT compared to untreated tumors (SUV mean : 2.83 ± 0.30 vs. 2.25 ± 0.41, P = 0.01, n = 5). Collagen deposition significantly increased in response to CRT (59 ± 9% vs. 30 ± 9%, P=0.0005 in treated vs. untreated tumors). Tumor and pancreas collagen content showed a positive direct correlation with SUV mean (R 2 = 0.54, P = 0.0007). Conclusions: This study demonstrates the specificity of 68 Ga-CBP8 PET to tumor type I collagen and its ability to differentiate responders from non-responders based on the dynamic changes of fibrosis in PDAC. The results highlight the potential use of collagen PET as a non-invasive tool for monitoring response to treatment in patients with PDAC., Competing Interests: Competing Interests: PC has equity in and is a consultant to Collagen Medical LLC, has equity in Reveal Pharmaceuticals Inc., and has research support from Transcode Therapeutics and Pliant Therapeutics. PC is a co-inventor of US Patent 10,471,162 which covers 68Ga-CBP8 and is assigned to the General Hospital Corporation. SE has research support from Sofie Biosciences, Telix, and Novartis Pharmaceuticals. ARP has held Equity in C2i Genomics, XGenomes, Cadex, Vionix and Parithera. In the last 36 months, she has served as an advisor/consultant for Eli Lilly, Mirati, Pfizer, Inivata, Biofidelity, Checkmate Pharmaceuticals, FMI, Guardant, Abbvie, Bayer, Delcath, Taiho, CVS, Value Analytics Lab, Seagen, Saga, AZ, Scare Inc, Illumina, Taiho, Hookipa, Kahar Medical, Xilio Therapeutics, Sirtex, Takeda, and Science For America. She receives fees from Up to Date. She has received travel fees from Karkinos Healthcare. She has been on the DSMC for a Roche study and on the Steering Committee for Exilixis. She has received research funding to the Institution from PureTech, PMV Pharmaceuticals, Plexxicon, Takeda, BMS, Mirati, Novartis, Erasca, Genentech, Daiichi Sankyo, Syndax, Revolution Medicine and Parthenon. UM is a co-founder, shareholder, and consultant (Scientific Advisory Board) of CytoSite BioPharma. TSH is a consultant for Synthetic Biologics, Novocure, Boston Scientific, Neogenomics, Merck, GSK, NextCure, serves on the advisory board of PanTher Therapeutics (Equity), and Lustgarten Foundation, and has received research funding from Taiho, Astra-Zeneca, BMS, GSK, ItraOp and Ipsen. GMB has sponsored research agreements through her institution with: Olink Proteomics, Teiko Bio, InterVenn Biosciences, Palleon Pharmaceuticals. She served on advisory boards for Iovance, Merck, Nektar Therapeutics, Novartis, and Ankyra Therapeutics. She consults for Merck, InterVenn Biosciences, Iovance, and Ankyra Therapeutics. She holds equity in Ankyra Therapeutics. Other authors declare that they have no competing interests., (© The author(s).)

Purpose: Radiation therapy (RT) is an effective treatment for unresectable cholangiocarcinoma (CC). Accurate tumor volume delineation is critical in achieving high rates of local control while minimizing treatment-related toxicity. This study compares 18F-FDG PET/MR to MR and CT for target volume delineation for RT planning. Methods: We retrospectively included 22 patients with newly diagnosed unresectable primary CC who underwent 18F-FDG PET/MR for initial staging. Gross tumor volume (GTV) of the primary mass (GTVM) and lymph nodes (GTVLN) were contoured on CT images, MR images, and PET/MR fused images and compared among modalities. The dice similarity coefficient (DSC) was calculated to assess spatial coverage between different modalities. Results: GTVMPET/MR (median: 94 ml, range 16–655 ml) was significantly greater than GTVMMR (69 ml, 11–635 ml) (p = 0.0001) and GTVMCT (96 ml, 4–564 ml) (p = 0.035). There was no significant difference between GTVMCT and GTVMMR (p = 0.078). Subgroup analysis of intrahepatic and extrahepatic tumors showed that the median GTVMPET/MR was significantly greater than GTVMMR in both groups (117.5 ml, 22–655 ml vs. 102.5 ml, 22–635 ml, p = 0.004 and 37 ml, 16–303 ml vs. 34 ml, 11–207 ml, p = 0.042, respectively). The GTVLNPET/MR (8.5 ml, 1–27 ml) was significantly higher than GTVLNCT (5 ml, 4–16 ml) (p = 0.026). GTVPET/MR had the highest similarity to the GTVMR, i.e., DSCPET/MR-MR (0.82, 0.25–1.00), compared to DSC PET/MR-CT of 0.58 (0.22–0.87) and DSCMR-CT of 0.58 (0.03–0.83). Conclusion: 18F-FDG PET/MR-based CC delineation yields greater GTVs and detected a higher number of positive lymph nodes compared to CT or MR, potentially improving RT planning by reducing the risk of geographic misses. [ABSTRACT FROM AUTHOR]

Background: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. Methods: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. Results: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. Conclusion: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed. [ABSTRACT FROM AUTHOR]

Purpose: Response criteria of glioblastoma after chemoradiation do not account for metabolic changes that occur after treatment. The purpose of this study is to evaluate the utility of positron emission tomography (PET) imaging with C11 methionine (MET) (MET-PET) for detecting changes that occur after chemoradiation therapy and the value of molecular biomarkers for predicting the magnitude of metabolic response.Methods and Materials: Patients with newly diagnosed glioblastoma undergoing standard chemoradiation treatment were enrolled in this prospective imaging study, with MET-PET scan performed within 3 days after surgical resection and again at 4 weeks after completion of chemoradiation. Near contemporaneous contrast-enhanced magnetic resonance imaging was performed within 2 weeks of each MET-PET scan. MET-PET imaging was analyzed for maximum standardized uptake value (SUV), SUVmean, and SUVvolume on a multimodality workstation.Results: A total of 18 patients underwent baseline postoperative MET-PET imaging, 14 of whom underwent postchemoradiation MET-PET imaging. Among those who showed residual MET-avid disease on immediate postoperative MET-PET scans and underwent postchemoradiation MET-PET imaging (n = 10), mean ΔSUVmax was -40% (range -100% to 0%), mean ΔSUVmean was -35% (range -100% to 0%), and mean ΔSUV volume was -64% (range -100% to 0%). The Δtumor/brain reference was -40% (range -100% to 0%) using SUVmax and -35% (range -100% to 0%) using SUVmean. In contrast, none of the T2-weighted images on contrast-enhanced magnetic resonance imaging showed a >25% reduction in abnormal T2/fluid-attenuated inversion recovery signal on visual assessment. ΔSUVmax, ΔSUVmean, and ΔSUVvolume correlated with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status (P = .01), but not with epidermal growth factor receptor or c-MET amplification status. All patients were IDH-1 wildtype.Conclusions: MET-PET scanning shows a significant decrease in metabolic signal at 1 month after chemoradiation compared with the immediate postoperative period, even when T2/fluid-attenuated inversion recovery changed little. MGMT promoter methylation status further predicts differential metabolic responses. MET-PET may be a useful tool for delineation of radiation targets and assessment of response. [ABSTRACT FROM AUTHOR]

Cancer cells are surrounded by a complex and highly dynamic tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), a critical component of TME, contribute to cancer cell proliferation as well as metastatic spread. CAFs express a variety of biomarkers, which can be targeted for detection and therapy. Most importantly, CAFs express high levels of fibroblast activation protein (FAP) which contributes to progression of cancer, invasion, metastasis, migration, immunosuppression, and drug resistance. As a consequence, FAP is an attractive theranostic target. In this review, we discuss the latest advancement in targeting FAP in oncology using theranostic biomarkers and imaging modalities such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), fluorescence imaging, and magnetic resonance imaging (MRI). [Display omitted] [ABSTRACT FROM AUTHOR]