99mTc-3PRGD2 SPECT to monitor early response to neoadjuvant chemotherapy in stage II and III breast cancer

Ji, Bin; Chen, Bin; Wang, Ting; Song, Yan; Chen, Minglong; Ji, Tiefeng; Wang, Xueju; Gao, Shi; Ma, Qingjie

doi:10.1007/s00259-015-3062-1

Cited by 13 publications

(13 citation statements)

References 36 publications

(51 reference statements)

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“…The pCR rate (13/41 31.7%) in this study was similar to that reported by previous studies [8,9]. The ΔT/B 1 of primary tumors showed a ROC-AUC (0.827) which was slightly lower than in a previous study (0.89) [23]. However, both that study and the present study found that the ΔT/B ratios for breast tumors in pCR group were higher than non-pCR group.…”

Section: Discussionsupporting

confidence: 88%

“…A limitation of our study was its limited number of patients, though the number was larger than previous study with 99m Tc-3PRGD 2 imaging [23]. Further multi-center clinical studies with larger patient numbers would be informative: for example, the tumor subtype analyses and cut-off points could be given further consideration if the patient cohort size permitted in more hospital.…”

Section: Discussionmentioning

confidence: 96%

“…We found in the present study that the pCR group showed higher ΔT/B than the non-pCR group among HER2-positive patients. Our previous study demonstrated that the 99m Tc-3PRGD 2 uptake rate of breast tumors was higher in HER2-positive patients than in luminal patients and triplenegative patients [23]. A clinical pathology study found a signi cant correlation between HER2 expression and microvessel density (MVD) in breast tumor specimens [40].…”

Section: Discussionmentioning

confidence: 99%

“…The changes of tumor integrin α v β 3 expression and tumor to normal background ratio (T/B) on 99m Tc-3PRGD 2 imaging in the squamous cell tumors signi cantly decreased in treatment group [22]. A study showed that 99m Tc-3PRGD 2 imaging can monitor the early pathological response of primary breast tumors to NAC [23]. However, the de nition of the pathological response of that study included minimal residual tumors, and it examined breast tumor pathological response only (i.e., no assessment of potential metastasis sites).…”

Section: Introductionmentioning

confidence: 99%

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Application of 99mTc-3PRGD2 Imaging for Early Prediction of Pathological Response to Neoadjuvant Chemotherapy in Breast Tumors and Axillary Lymph Nodes

Chen

Lin

et al. 2020

Preprint

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Background and PurposeTechnetium 99m-dimeric cyclic RGD peptides with three polyethylene glycol spacers (99mTc-3PRGD2) had a good performance for diagnosing breast cancer. The prospective study was to assess the performance of 99mTc-3PRGD2 tumor imaging for predicting pathological complete response (pCR) outcomes to neoadjuvant chemotherapy (NAC) in breast cancer patients.Materials and MethodsForty-one patients were examined using both 99mTc-3PRGD2 and 18F-fluoro-deoxy-glucose (18F-FDG) imaging before NAC (baseline), and after the first and fifth NAC cycle. The tumor-to-background (T/B) ratios for 99mTc-3PRGD2 imaging and the maximum standardized uptake values (SUVmax) from the 18F-FDG imaging in breast tumors and axillary lymph node (ALN) metastases were separately calculated and analyzed—based on receiver operating characteristic (ROC) analysis. ResultsFinally, pCR was achieved in 13 of 41 patients after NAC. The area under curve (AUC) of T/B changes (ΔT/B) in breast tumors for predicting pCR after first and fifth cycle were 0.827 and 0.687, and 0.859 and 0.778 in ALN metastases, respectively. For SUVmax changes (ΔSUVmax), the ROC-AUC were 0.859 and 0.713, as well as 0.572 and 0.802, respectively. In breast tumors, the AUCs of ΔT/B1 and ΔSUVmax1 had no significant difference (P > 0.05). However, the AUC of ΔT/B1 was significantly higher than for ΔSUVmax1 in ALN metastases (Z = 2.10, P = 0.035). Additionally, the T/B1 trends for breast tumor and ALN in pCR group were higher than for non-pCR group in HER2-positive patients (P﹤0.05). ConclusionsCompared with 18F-FDG imaging, our study shows that use of 99mTc-3PRGD2 imaging offered a similar level of predictive performance for breast cancer pCR to NAC, and early T/B1 trends of ALN showed an higher performance for predicting pCR.Trial RegistrationClinicalTrials.gov ID: NCT02742168.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Application of 99mTc-3PRGD2 Imaging for Early Prediction of Pathological Response to Neoadjuvant Chemotherapy in Breast Tumors and Axillary Lymph Nodes

Chen

Lin

et al. 2020

Preprint

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“…However, there is still no appropriate imaging modality to monitor the efficacy of anti-angiogenic therapy. Research has shown that 99m Tc-3PRGD 2 can be applied to guide anti-angiogenic therapy by visualizing and quantifying the expression level of αvβ3 [18, 31]. Thus, 99m Tc-3PRGD 2 imaging has the potential to select suitable patients who could benefit from sorafenib chemotherapy and supply an objective basis for its curative effect.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of 99mTc-3PRGD2 integrin receptor imaging in hepatocellular carcinoma tumour-bearing mice: comparison with 18F-FDG metabolic imaging

et al. 2017

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ObjectiveOur study was designed to explore the utility of 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of 99mTc-3PRGD2 integrin receptor imaging and 2-18-fluoro-2-deoxy-d-glucose (18F-FDG) metabolic imaging in a nude mouse model.Methods 99mTc-3PRGD2 was synthesized using a HYNIC-3PRGD2 lyophilized kit with 99mTcO4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 107/ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of 99mTc-3PRGD2. Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of 99mTc-3PRGD2, to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of 99mTc-3PRGD2 and 37 MBq of 18F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of 99mTc-3PRGD2 and 18F-FDG.ResultsThe biodistribution study first validated that the tumour uptake of 99mTc-3PRGD2 at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under 99mTc-3PRGD2 SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that 99mTc-3PRGD2 integrin receptor imaging was more sensitive than 18F-FDG metabolic imaging for the detection of early stage HCC, meanwhile the tumour uptake of 99mTc-3PRGD2 was consistently higher than that of 18F-FDG. However, as tumour necrosis further increased in HCC tissues, the uptake of 18F-FDG was higher than that of 99mTc-3PRGD2.ConclusionOur study demonstrated that 99mTc-3PRGD2 is a valuable tumour molecular probe for the detection of early stage HCC compared with 18F-FDG, meriting further investigation of 99mTc-3PRGD2 as a novel SPECT tracer for tumour imaging.

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Targeted Nanodrugs to Destroy the Tumor Extracellular Matrix Barrier for Improving Drug Delivery and Cancer Therapeutic Efficacy

Chen

Xia

et al. 2023

Mol. Pharmaceutics

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One of the main reasons why most cancer patients do not respond well to chemotherapy is that drugs cannot accumulate in tumors at an optimal dose, eventually resulting in failure to prevent cancer cell growth. To improve drug delivery efficiency, we engineered a highly efficient tumor-targeted and stroma-breaking nanocarrier by the modification of iron oxide nanoparticles (IONPs) with a tumor-targeting peptide c(RGDyK) and a hyaluronidase (HAase) on the surface. The yielding nanocomplex, c(RGDyK)-HAase-IONP, targeted the tumor by binding integrin αvβ3 and went deeply into the tumors by the degradation of hyaluronic acid (HA), which was highly expressed in the tumor extracellular matrix (ECM). Good biostability and a low pH preferred drug release profile were characterized for c(RGDyK)-HAase-IONP carrying DOX in vitro. c(RGDyK)-HAase-IONP showed an improved tumor-targeting (2.5 times higher) effect after intravenous injection in the MC38 tumor-bearing mice model, as determined by whole-body fluorescence imaging compared to the non-targeted IONPs without HAase. After 5 systemic treatments, c(RGDyK)-HAase-IONP/DOX (5 mg/kg of equivalent dose of DOX) significantly inhibited MC38 tumor growth (22.1 ± 7.4 times relative to the non-treated group). Elevated apoptosis and reduced proliferation in the tumor cell were detected in the c(RGDyK)-HAase-IONP/DOX treated tumors compared to the control groups. Overall, the highly efficient targeted nanocarrier c(RGDyK)-HAase-IONP demonstrated tremendous potency for improving drug delivery and tumor therapy efficacy by targeted degradation of the dense HA barrier in the tumor ECM. We determined that such a tumor stroma–degrading nanosystem was capable of reducing tumor recurrence and drug resistance and could ultimately improve clinical tumor treatment responses.

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99mTc-3PRGD2 SPECT to monitor early response to neoadjuvant chemotherapy in stage II and III breast cancer

Abstract: (99m)Tc-3PRGD2 SPECT seems to be useful for determining the pathological tumor response in patients with stage II or III breast cancer undergoing NCT, especially those with the HER-2-positive subtype.

Cited by 13 publications

References 36 publications

Application of 99mTc-3PRGD2 Imaging for Early Prediction of Pathological Response to Neoadjuvant Chemotherapy in Breast Tumors and Axillary Lymph Nodes

Application of 99mTc-3PRGD2 Imaging for Early Prediction of Pathological Response to Neoadjuvant Chemotherapy in Breast Tumors and Axillary Lymph Nodes

Evaluation of 99mTc-3PRGD2 integrin receptor imaging in hepatocellular carcinoma tumour-bearing mice: comparison with 18F-FDG metabolic imaging

Targeted Nanodrugs to Destroy the Tumor Extracellular Matrix Barrier for Improving Drug Delivery and Cancer Therapeutic Efficacy

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