68Ga-Labeled Cystine Knot Peptide Targeting Integrin αvβ6 for Lung Cancer PET Imaging

Ren, Jingyun; Zhu, Shiyu; Zhang, Guojin; Tan, Xiaoyue; Qiu, Ling; Lin, Jianguo; Jiang, Lei

doi:10.1021/acs.molpharmaceut.2c00313

Cited by 5 publications

(4 citation statements)

References 32 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The α v β 6 integrin has been identified as a significant marker for lung cancer, typically linked to a worse prognosis. Ren et al [ 86 ] created the cystine-knot peptide R01-MG, intended for PET imaging of α v β 6 -positive lung cancer cases. R01-MG was crafted through solid-phase peptide synthesis techniques and labeled with [ 68 Ga]Ga following its conjugation with DOTA, a cyclic compound designed for radiolabeling.…”

Section: Lung Cancer Targeting Probesmentioning

confidence: 99%

“…In vivo PET scans and distribution studies showed that [ 68 Ga]Ga-DOTA-R01-MG was characterized by its quick and efficient uptake in α v β 6-expressing lung tumors, along with swift elimination from non-cancerous tissues, which enhanced the contrast between tumor and normal tissue in images. Conversely, the absence of significant uptake of [ 68 Ga]Ga-DOTA-R01-MG in α v β 6 -negative lung cancer models underscored the probe's targeted specificity towards the α v β 6 integrin [86]. Flechsig et al (2019) investigated the clinical value of SFITGv6, a specific α v β 6 integrin peptide, for the targeted diagnosis of NSCLC.…”

Section: Lung Cancer Targeting Probesmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Imaging for Lung Cancer: Exploring Small Molecules, Peptides, and Beyond in Radiolabeled Diagnostics

Ekinci,

Magne,

Alencar

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

It is evident that radiolabeled drug delivery systems hold great promise in the field of lung cancer management. The combination of therapeutic agents with radiotracers not only allows for precise localization within lung tumors but also enables real-time monitoring of drug distribution. This approach has the potential to enhance targeted therapy and improve patient outcomes. The integration of advanced imaging modalities, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), has played a crucial role in the non-invasive tracking of radiolabeled drugs. These techniques provide valuable insights into drug pharmacokinetics, biodistribution, and tumor-targeting efficiency, offering clinicians the ability to personalize treatment regimens. The comprehensive analysis of preclinical and clinical studies presented in this review underscores the progress made in the field. The evidence suggests that radiolabeled drug delivery systems have the potential to revolutionize oncology by offering precise, targeted, and image-guided therapeutic interventions for lung cancer. This innovative approach not only enhances the effectiveness of treatment but also contributes to the development of personalized medicine strategies, tailoring interventions to the specific characteristics of each patient’s cancer. The ongoing research in this area holds promise for further advancements in lung cancer management, potentially leading to improved outcomes and quality of life for patients.

show abstract

Section: Lung Cancer Targeting Probesmentioning

confidence: 99%

Section: Lung Cancer Targeting Probesmentioning

confidence: 99%

Molecular Imaging for Lung Cancer: Exploring Small Molecules, Peptides, and Beyond in Radiolabeled Diagnostics

Ekinci,

Magne,

Alencar

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…Cyclic peptides: A20FMD2 [210] , SFITGv6 [211] , SFLAP3 [212] , c(XAmpRGDX) [213] , c(FRGDLA-Fp [NMe] K) [214] Peptides: RGDLATLRNL [215] , H2009.1 [216] Small molecules: GSK3008348 [217] , PLN-74809 (dual α V β 1 /α V β 6 inhibitor) [191] , arylmorpholines [218] Other: Knotting peptides [219] α V β 8…”

Section: Integrinmentioning

confidence: 99%

Small molecule– and peptide–drug conjugates addressing integrins: A story of targeted cancer treatment

Paulus,

Sewald

2024

Journal of Peptide Science

View full text Add to dashboard Cite

Targeted cancer treatment should avoid side effects and damage to healthy cells commonly encountered during traditional chemotherapy. By combining small molecule or peptidic ligands as homing devices with cytotoxic drugs connected by a cleavable or non‐cleavable linker in peptide–drug conjugates (PDCs) or small molecule–drug conjugates (SMDCs), cancer cells and tumours can be selectively targeted. The development of highly affine, selective peptides and small molecules in recent years has allowed PDCs and SMDCs to increasingly compete with antibody‐drug conjugates (ADCs). Integrins represent an excellent target for conjugates because they are overexpressed by most cancer cells and because of the broad knowledge about native binding partners as well as the multitude of small‐molecule and peptidic ligands that have been developed over the last 30 years. In particular, integrin αVβ3 has been addressed using a variety of different PDCs and SMDCs over the last two decades, following various strategies. This review summarises and describes integrin‐addressing PDCs and SMDCs while highlighting points of great interest.

show abstract

“…Several PET tracers, such as arginine-glycine-aspartic (RGD) derivatives targeted-integrin αvβ3 receptors, have been involved in clinical trials and have shown good application value in many types of solid tumors. − As a subtype of the integrin family, integrin α6 is expressed on the surface of the cells and acts as a regulator of a variety of cellular functions that are critical to the occurrence, development, and metastasis of solid tumors . Various researchers have reported the potential clinical application value of integrin α6 in many tumor models including for hepatocellular carcinoma (HCC), breast cancer, lung cancer, and colorectal cancer . Richard H. Kimura et al developed an integrin αvβ6 cystine knot PET tracer that can effectively detect multiple cancers in different parts of the body .…”

Section: Introductionmentioning

confidence: 99%

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer

Chen

et al. 2023

Mol. Pharmaceutics

View full text Add to dashboard Cite

Integrin α6 has been considered a promising biomarker, is overexpressed in many tumors, and plays a vital role in tumor formation, recurrence, and metastasis. In this study, we identified a novel high-affinity integrin α6-targeted peptide named RD2 (Arg-Trp-Tyr-Asp-PEG4)2-Lys-Lys and developed a 18F-radiolabeled peptide tracer ([18F]-AlF-NOTA-RD2) and evaluated its potential application in positron emission tomography (PET) imaging of pancreatic cancer. [18F]-AlF-NOTA-RD2 was produced using GMP (Good Manufacturing Practice of Medical Products)-compliant automatic radiosynthesis on a single GE FASTLab2 cassette-type synthesis module. The stability of [18F]-AlF-NOTA-RD2 was analyzed in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). The cell uptake assay of the tracer was assessed using PANC-1 cells. In addition, small-animal PET imaging and biodistribution studies of [18F]-AlF-NOTA-RD2 were performed in pancreatic cancer subcutaneous tumor-bearing mice. The PET tracer [18F]-AlF-NOTA-RD2 was obtained with a radiochemical yield of 23.7 ± 4.7%, radiochemical purity of >99%, and molar activity of 165.7 ± 59.1 GBq/μmol. [18F]-AlF-NOTA-RD2 exhibited good in vitro stability in PBS and FBS. LogP octanol water value for the tracer was −2.28 ± 0.05 (n = 3). The binding affinity of RD2 to the integrin α6 protein (K d = 0.13 ± 3.65 μM, n = 3) was significantly higher than that of the RWY (CRWYDENAC) (K d = 6.97 ± 1.44 μM, n = 3). Small-animal PET imaging and biodistribution also revealed that [18F]-AlF-NOTA-RD2 displayed rapid and good tumor uptake and lower liver background uptake in PANC-1 tumor-bearing mice. [18F]-AlF-NOTA-RD2 showed significant radioactivity accumulation in tumors and was successfully blocked by NOTA-RD2. Compared with [18F]-FDG, [18F]-AlF-NOTA-RD2 PET imaging and biodistribution studies in PANC-1 xenograft tumor-bearing mice confirmed a good tumor-to-muscle ratio (8.69 ± 2.03 vs 1.41 ± 0.23, respectively) at 0.5 h and (2.99 ± 3.02 vs 1.43 ± 0.17, respectively) at 1 h post injection. Autoradiography of human pancreatic cancer tumor tissues further confirmed high accumulation of [18F]-AlF-NOTA-RD2. In summary, we developed an optimized integrin α6-targeted imaging tracer and obtained high radioactivity products with a cassette-type synthesis module; moreover, the tracer exhibited good binding affinity with integrin α6 and good target specificity for PANC-1 cells in xenograft pancreatic tumor-bearing mice, demonstrating its promising application as a noninvasive PET radiotracer of integrin α6 expression in pancreatic cancer.

show abstract

⁶⁸Ga-Labeled Cystine Knot Peptide Targeting Integrin α_vβ₆ for Lung Cancer PET Imaging

Cited by 5 publications

References 32 publications

Molecular Imaging for Lung Cancer: Exploring Small Molecules, Peptides, and Beyond in Radiolabeled Diagnostics

Molecular Imaging for Lung Cancer: Exploring Small Molecules, Peptides, and Beyond in Radiolabeled Diagnostics

Small molecule– and peptide–drug conjugates addressing integrins: A story of targeted cancer treatment

Automated Synthesis and Preclinical Evaluation of Optimized Integrin α6-Targeted Positron Emission Tomography Imaging of Pancreatic Cancer

Contact Info

Product

Resources

About