Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice

Lo, Wei-Lin; Lo, Shih-Wei; Chen, Su-Jung; Chen, Ming-Wei; Huang, Yiyun; Chang, Cheng-Yen; Li, Ming-Hsin

doi:10.3390/ijms22115459

Cited by 9 publications

(4 citation statements)

References 42 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combination of albumin-binding moieties derived from Evans Blue dye and 4-(piodophenyl)butyric acid with targeted radiopharmaceuticals demonstrates prolonged blood circulation and increased tumor uptake. The conjugation with truncated EB resulted in improved tumor uptake and pharmacokinetics using 177 Lu-labeled tumor targeting vectors specific for somatostatin receptors (EB-TATE), integrin α v β 3 (EB-cRGD), prostatespecific membrane antigen (EB-PSMA-617), and glucagon-like peptide-1 receptor (EBexendin-4) [24,[30][31][32]. On the other hand, the introduction of a 4-(p-iodophenyl)butyric acid derivatives showed promising in vivo results using [ 177 Lu]Lu-folates-cm10 for radionuclide therapy of folate receptor α (FR)-positive cancer and [ 177 Lu]-PSMA-ALB-2 for prostate cancer therapy [33,34].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy of 177Lu-Labeled A20FMDV2 Peptides Targeting ανβ6

et al. 2022

View full text Add to dashboard Cite

Integrin ανβ6 promotes migration and invasion of cancer cells, and its overexpression often correlates with poor survival. Therefore, targeting ανβ6 with radioactive peptides would be beneficial for cancer imaging and therapy. Previous studies have successfully developed radiotracers based on the peptide A20FMDV2 that showed good binding specificity for ανβ6. However, one concern of these ανβ6 integrin-targeting probes is that their rapid blood clearance and low tumor uptake would preclude them from being used for therapeutic purposes. In this study, albumin binders were used to increase tumor uptake for therapeutic applications while the non-albumin peptide was evaluated as a potential positron emission tomography (PET) imaging agent. All peptides used the DOTA chelator for radiolabeling with either 68Ga for imaging or 177Lu for therapy. PET imaging with [68Ga]Ga-DOTA-(PEG28)2-A20FMDV2 revealed specific tumor uptake in ανβ6-positive tumors. Albumin-binding peptides EB-DOTA-(PEG28)2-A20FMDV2 and IBA-DOTA-(PEG28)2-A20FMDV2 were radiolabeled with 177Lu. Biodistribution studies in normal mice showed longer blood circulation times for the albumin binding peptides compared to the non-albumin peptide. Therapy studies in mice demonstrated that both 177Lu-labeled albumin binding peptides resulted in significant tumor growth inhibition. We believe these are the first studies to demonstrate the therapeutic efficacy of a radiolabeled peptide targeting an ανβ6-positive tumor.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy of 177Lu-Labeled A20FMDV2 Peptides Targeting ανβ6

et al. 2022

View full text Add to dashboard Cite

show abstract

“…These results highlight the interest in 68 Ga-radiolabeled RGD for imaging of αvβ3-expressing GBM. Another novel long-circulation integrin-targeted molecule, [ 111 In]DOTA-EB-cRGDfK, showed significant tumor accumulation with high tumor-to-background ratio at 24h post-injection in U87-MG xenografts [ 101 ]. These radiotracers deserve further clinical investigations to confirm their potential.…”

Section: Anti-integrin-αvβ3 Agents For Anti-cancer Therapymentioning

confidence: 99%

Integrin-αvβ3 as a Therapeutic Target in Glioblastoma: Back to the Future?

et al. 2022

View full text Add to dashboard Cite

Glioblastoma (GBM), the most common primary malignant brain tumor, is associated with a dismal prognosis. Standard therapies including maximal surgical resection, radiotherapy, and temozolomide chemotherapy remain poorly efficient. Improving GBM treatment modalities is, therefore, a paramount challenge for researchers and clinicians. GBMs exhibit the hallmark feature of aggressive invasion into the surrounding tissue. Among cell surface receptors involved in this process, members of the integrin family are known to be key actors of GBM invasion. Upregulation of integrins was reported in both tumor and stromal cells, making them a suitable target for innovative therapies targeting integrins in GBM patients, as their impairment disrupts tumor cell proliferation and invasive capacities. Among them, integrin-αvβ3 expression correlates with high-grade GBM. Driven by a plethora of preclinical biological studies, antagonists of αvβ3 rapidly became attractive therapeutic candidates to impair GBM tumorigenesis. In this perspective, the advent of nuclear medicine is currently one of the greatest components of the theranostic concept in both preclinical and clinical research fields. In this review, we provided an overview of αvβ3 expression in GBM to emphasize the therapeutic agents developed. Advanced current and future developments in the theranostic field targeting αvβ3 are finally discussed.

show abstract

“…The cell adhesion sequence of fibronectin, arginine-glycine-aspartic acid (RGD) tripeptide, has a high affinity for integrin proteins [14] . As integrin proteins are overexpressed in the vasculature of tumor microenvironments, RGD peptides can be immobilized on the surface of nanocarriers for targeting purposes [15] .…”

Section: Introductionmentioning

confidence: 99%