scholarly journals Effect of Peptide Receptor Radionuclide Therapy in Combination with Temozolomide against Tumor Angiogenesis in a Glioblastoma Model

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 5029
Author(s):  
Sang Hee Lee ◽  
Ji Young Choi ◽  
Jae Ho Jung ◽  
In Ho Song ◽  
Hyun Soo Park ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Radionuclide Therapy ◽  
Tumor Volume ◽  
Therapeutic Potential ◽  
Combined Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Treated Group ◽  
Peptide Receptor ◽  
Vehicle Treated Group

Cell adhesion receptor integrin avb3 is a promising biomarker for developing tumor-angiogenesis targeted theranostics. In this study, we aimed to examine the therapeutic potential of peptide receptor radionuclide therapy (PRRT) with 188Re-IDA-D-[c(RGDfK)]2 (11.1 MBq). The results showed that the tumor volume was significantly decreased by 81% compared with the vehicle-treated group in U87-MG xenografts. The quantitative in vivo anti-angiogenic responses of PRRT were obtained using 99mTc-IDA-D-[c(RGDfK)]2 SPECT and corresponded to the measured tumor volume. PRRT combined with temozolomide (TMZ) resulted in a 93% reduction in tumor volume, which was markedly greater than that of each agent used individually. In addition, histopathological characterization showed that PRRT combined with TMZ was superior to PRRT or TMZ alone, even when TMZ was used at half dose. Overall, our results indicated that integrin-targeted PRRT and TMZ combined therapy might be a new medical tool for the effective treatment of glioblastoma.

scholarly journals In Vivo Instability of 177Lu-DOTATATE During Peptide Receptor Radionuclide Therapy

2020 ◽  
Vol 61 (9) ◽  
pp. 1337-1340
Author(s):  
Mark Lubberink ◽  
Helena Wilking ◽  
Amalia Öst ◽  
Ezgi Ilan ◽  
Mattias Sandström ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Peptide Receptor

Reduction of chronic allograft nephropathy by inhibition of extracellular signal-regulated kinase 1 and 2 signaling

2008 ◽  
Vol 295 (3) ◽  
pp. F672-F679 ◽  
Author(s):  
Shuang Wang ◽  
Jifu Jiang ◽  
Qiunong Guan ◽  
Hao Wang ◽  
Christopher Y. C. Nguan ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Mek Inhibitor ◽  
Treated Group ◽  
Chronic Allograft Nephropathy ◽  
Beneficial Effects ◽  
Extracellular Signal ◽  
Vehicle Treated Group

Chronic allograft nephropathy (CAN), the most common cause of late kidney allograft failure, is not effectively prevented by immunosuppressive regimens. Activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) via MEK mediates actions of various growth factors, including transforming growth factor (TGF)-β1, which plays a key role in CAN. Hence, we tested the therapeutic potential of MEK-ERK1/2 signaling disruption to prevent CAN. Kidneys from C57BL/6J (H-2b) mice were transplanted to bilaterally nephrectomized BALB/c (H-2d) mice. At 14 days after transplantation, the recipients were subjected to 28 days of treatment with the MEK inhibitor CI-1040. All six CI-1040-treated allografts survived, while two of seven grafts in the vehicle-treated group were lost. At the end of the experiment, the function and structure of grafts in the CI-1040-treated group were significantly preserved, as indicated by lower levels of serum creatinine or blood urea nitrogen than in the vehicle-treated group [30 ± 6 vs. 94 ± 39 μM creatinine ( P = 0.0015) and 22 ± 8 vs. 56 ± 25 mM BUN ( P = 0.0054)] and reduced CAN in the CI-1040-treated group compared with vehicle controls (CAN score = 4.2 vs. 10.3, P = 0.0119). The beneficial effects induced by CI-1040 were associated with reduction of ERK1/2 phosphorylation and TGFβ1 levels in grafts. Also, CI-1040 potently suppressed not only TGFβ biosynthesis in kidney cell cultures but also antiallograft immune responses in vitro and in vivo. Our data suggest that interference of MEK-ERK1/2 signaling with a pharmacological agent (e.g., CI-1040) has therapeutic potential to prevent CAN in kidney transplantation.

scholarly journals Dosimetric evaluation of receptor-heterogeneity on the therapeutic efficacy of peptide receptor radionuclide therapy: correlation with DNA damage induction and in vivo survival

2021 ◽  
pp. jnumed.121.262122
Author(s):  
Giulia Tamborino ◽  
Julie Nonnekens ◽  
Marijke De Saint-Hubert ◽  
Lara Struelens ◽  
Danny Feijtel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Therapeutic Efficacy ◽  
Radionuclide Therapy ◽  
Peptide Receptor Radionuclide Therapy ◽  
Peptide Receptor

Feasibility and Therapeutic Potential of Combined Peptide Receptor Radionuclide Therapy With Intensive Chemotherapy for Pediatric Patients With Relapsed or Refractory Metastatic Neuroblastoma

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Gholamreza Fathpour ◽  
Esmail Jafari ◽  
Arman Hashemi ◽  
Habibollah Dadgar ◽  
Mahdi Shahriari ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Pediatric Patients ◽  
Therapeutic Potential ◽  
Peptide Receptor Radionuclide Therapy ◽  
Intensive Chemotherapy ◽  
Peptide Receptor

177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: Dose Response in Small Intestinal Neuroendocrine Tumors

2019 ◽  
Vol 110 (7-8) ◽  
pp. 662-670 ◽  
Author(s):  
Ulrika Jahn ◽  
Ezgi Ilan ◽  
Mattias Sandström ◽  
Ulrike Garske-Román ◽  
Mark Lubberink ◽  
...  
Keyword(s):  
Dose Response ◽  
Radionuclide Therapy ◽  
Tumor Volume ◽  
Absorbed Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tumor Diameter ◽  
Tumor Shrinkage ◽  
Peptide Receptor ◽  
Recist 1.1 ◽  
Small Intestinal

Introduction: Peptide receptor radionuclide therapy (PRRT) has during the last few years been frequently used in patients with progressive, disseminating, well-differentiated neuroendocrine tumors (NETs). Objective: To study whether the absorbed dose in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage. Materials and Methods: Dosimetry for 1 tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT 1, 4, and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume, and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response. Results: At the time of best response with respect to tumor diameter and volume shrinkage, the median absorbed dose was 128.6 Gy (range 28.4–326.9) and 140 Gy (range 50.9–487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered radioactivity and the tumor volume shrinkage (p = 0.01) and between the administered radioactivity and RECIST 1.1 response (p = 0.01). Conclusions: It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs.

Feasibility and Therapeutic Potential of Peptide Receptor Radionuclide Therapy for High-Grade Gliomas

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Reza Nemati ◽  
Hossein Shooli ◽  
Seyed Javad Rekabpour ◽  
Hojjat Ahmadzadehfar ◽  
Esmail Jafari ◽  
...  
Keyword(s):  
Radionuclide Therapy ◽  
Therapeutic Potential ◽  
Peptide Receptor Radionuclide Therapy ◽  
High Grade ◽  
Peptide Receptor ◽  
High Grade Gliomas
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