Cancer Research and Treatment

Endocrine cancer

Phase 1 Study of No-Carrier Added ¹⁷⁷Lu-DOTATATE (SNU-KB-01) in Patients with Somatostatin Receptor–Positive Neuroendocrine Tumors: The First Clinical Trial of Peptide Receptor Radionuclide Therapy in Korea: Hyun Gee Ryoo, Minseok Suh, Keon Wook Kang, Dae-Won Lee, Sae-Won Han, Gi Jeong Cheon; Cancer Res Treat. 2023;55(1):334-343. Published online April 22, 2022; DOI: https://doi.org/10.4143/crt.2021.1022

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Purpose
To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) ¹⁷⁷Lu-labeled DOTATATE.
Materials and Methods
Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.55 GBq (n=3) and 7.40 GBq (n=4). We assessed the incidence of dose-limiting toxicity (DLT) and adverse event, absorbed dose of kidneys and bone marrow, and objective tumor response.
Results
Seven patients completed 4 cycles (21.3-30.1 GBq total dose) of SNU-KB-01. The mean absorbed doses to kidneys and bone marrow were 0.500 mGy/MBq and 0.053 mGy/MBq, respectively, and the total body effective dose was 0.115 mSv/MBq. No DLT was observed and the maximum tolerated dose was 7.40 GBq/cycle. Grade 3 thrombocytopenia occurred in one patient, but no other grade 3 or 4 major hematologic or renal toxicity was observed. The best objective response to SNU-KB-01 was partial response. Overall response rate was 42.9% and disease control rate was 85.7%.
Conclusion
Treatment with 4 cycles of SNU-KB-01 was well tolerated and resulted in control of disease in most of the patients. Our results indicate SNU-KB-01, an NCA ¹⁷⁷Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.

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Peptide-drug conjugates: A new paradigm for targeted cancer therapy
Mo Wang, Jiawei Liu, Mingjing Xia, Libinghan Yin, Ling Zhang, Xifu Liu, Yu Cheng
European Journal of Medicinal Chemistry.2024; 265: 116119. CrossRef
Electrochemical separation and purification of no-carrier-added 177Lu for radiopharmaceutical preparation: Translation from bench to bed
Sourav Patra, Rubel Chakravarty, Khajan Singh, K.V. Vimalnath, Sudipta Chakraborty
Chemical Engineering Journal Advances.2023; 14: 100444. CrossRef

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Gastrointestinal cancer

Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer: Jeesun Yoon, Seo Young Kang, Kyung-Hun Lee, Gi Jeong Cheon, Do-Youn Oh; Cancer Res Treat. 2021;53(2):471-479. Published online October 22, 2020; DOI: https://doi.org/10.4143/crt.2020.577

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Purpose
Hypoxia is widely known as one of the mechanisms of chemoresistance and as an environmental condition which triggers invasion and metastasis of cancer. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard conjugated with 2-nitroimidazole. Biliary tract cancer (BTC) is known to contain large hypoxic area. This study evaluated the efficacy and safety of evofosfamide as a second-line treatment of advanced BTC.
Materials and Methods
Patients received evofosfamide at a dose of 340 mg/m² on days 1, 8, and 15 of every 28-day cycle. Primary end-point was progression-free survival (PFS) rate at 4-months (4m-PFSR). Secondary end-points included overall survival (OS), PFS, disease control rate (DCR), metabolic response by ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), hypoxic parameters evaluated by ¹⁸F-fluoromisonidazole (FMISO) PET and toxicity.
Results
Twenty patients were treated with evofosfamide, with 16 response-evaluable patients. There was no objective response; stable disease was observed in nine patients, with a DCR of 56.25%. 4m-PFSR was 40.6%. Median PFS was 3.60 months (95% confidence interval [CI], 1.68 to 5.52). Median OS was 6.37 months (95% CI, 3.94 to 8.79). Reduction of tumor metabolic activity was observed in eight of 15 patients (53.3%). High baseline hypoxic parameters were associated with poor PFS. Change of hypoxic parameters between pretreatment and post-treatment reflected hypoxic-activated drug response. There was no treatment-related death.
Conclusion
Evofosfamide as second-line treatment of advanced BTC showed acceptable safety and comparable efficacy to other agents. Changes in volumetric parameters measured with FMISO PET, showing the degree of tumor hypoxia, reflected the response to evofosfamide based on the mode of action.

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Functional Imaging of Hypoxia: PET and MRI
Ryan C. Perez, DaeHee Kim, Aaron W. P. Maxwell, Juan C. Camacho
Cancers.2023; 15(13): 3336. CrossRef
Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors
Marcel A. Schneider, Michael Linecker, Ralph Fritsch, Urs J. Muehlematter, Daniel Stocker, Bernhard Pestalozzi, Panagiotis Samaras, Alexander Jetter, Philipp Kron, Henrik Petrowsky, Claude Nicolau, Jean-Marie Lehn, Bostjan Humar, Rolf Graf, Pierre-Alain C
Nature Communications.2021;[Epub] CrossRef

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FDG-PET in Mediastinal Nodal Staging of Non-small Cell Lung Cancer: Correlation of False Results with Histopathologic Finding: Hee Jong Baek, Jin Haeng Chung, Jong Ho Park, Jae Ill Zo, Gi Jeong Cheon, Chang Woon Choi, Sang Moo Lim, Soo Yong Choi, Jong Myeon Hong, Jang Soo Hong; Cancer Res Treat. 2003;35(3):232-238. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.232

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PURPOSE
Mediastinal staging of non-small cell lung cancer can be markedly improved by FDG-PET scan, but the problem of false staging of mediastinal nodes by PET scan in non-small cell lung cancer has not yet been overcome. The aim of this study was to identify the mechanism underlying the false staging of mediastinal nodes by FDG-PET in the case of non-small cell lung cancer. MATERIALS AND METHODS: To evaluate the factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was performed in 62 patients with NSCLC. GLUT-1 expression was studied by immunohistochemistry of the mediastinal nodes (n=111, true positive 31, true negative 41, false positive 27, false negative 12) using the anti-GLUT-1 antibody. The size, percentage of tumor (tumor ratio), labeling index (rate of stained tumor), staining intensity of the tumor, level of follicular hyperplasia, and staining intensity of the follicle center in the mediastinal node were also studied. RESULTS: There was no significant difference in size among the 4 nodal groups (TP, TN, FP, FN), nor in the tumor ratio of the metastatic nodes between the TP and FN groups. The labeling index and staining intensity of the TP group were higher than those of the FN group (Mann-Whitney test, p=.001, p=.007) in the case of the metastatic nodes. The level of follicular hyperplasia of the FP group was higher than that of the TN group in the case of the non-metastatic nodes (p=.000). CONCLUSION: These results suggest that in mediastinal staging of non-small cell lung cancer by FDG-PET, the FN node is associated with low uptake of FDG due to low expression of GLUT-1, and that the FP node is associated with a high level of follicular hyperplasia as a result of there being a reactive change to an inflammatory and/or immune reaction. This is the first report on the mechanism underlying the false results that are sometimes obtained, and which constitute a major problem in the clinical application of FDG-PET to the mediastinal staging of non-small cell lung cancer.

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Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer
Hongsik Kim, Song-Yi Choi, Tae-Young Heo, Kyeong-Rok Kim, Jisun Lee, Min Young Yoo, Taek-Gu Lee, Joung-Ho Han
World Journal of Clinical Cases.2024; 12(5): 931. CrossRef
Associations between GLUT expression and SUV values derived from FDG-PET in different tumors—A systematic review and meta analysis
Hans-Jonas Meyer, Andreas Wienke, Alexey Surov, Pankaj K Singh
PLOS ONE.2019; 14(6): e0217781. CrossRef

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Correlation of GLUT-1 Expression and F-18-FDG Uptake on Positron Emission Tomography in Breast Carcinoma: Gi Jeong Cheon, June Key Chung, Bo Kwang Kim, Yong Jin Lee, Dong Young Noh, Ja June Jang, Jeong Seok Yeo, Jae Min Jeong, Dong Soo Lee, Myung Chul Lee; J Korean Cancer Assoc. 2000;32(6):1067-1074.

Abstract PDF: PURPOSE
Fluorine-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) has been proven to be useful in the detection of breast cancer. However, the degree of FDG uptake was variable. In this study, we evaluated the relationship between glucose transporter-1 (GLUT-1) expression with the FDG uptake in patients with breast cancer.
MATERIALS AND METHODS
15 patients with proven breast cancer underwent F-18-FDG PET. After surgical resection, anti-GLUT-1 immunohistochemical staining was performed in tumor tissues to measure the GLUT-1 expression. We evaluated the correlation between semi-quantitative FDG uptake by standardized uptake value (SUV) and GLUT-1 expression.
RESULTS
In total 15 patients, there was no significant correlation between SUV and GLUT-1 expression. We separated the patients into two groups according to the tumor size. In the group of large tumor (short diameter > or =2 cm), there was no significant correlation. However, in the group of small tumor (short diameter <2 cm), there was a significant correlation between the FDG uptake and GLUT-1 expression (rho=0.812, p=0.047).
CONCLUSION
GLUT-1 expression can influence the FDG uptake in the small breast cancers. For large breast cancers, other factors as well as GLUT-1 expression may influence the FDG uptake.

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