Dual-Modal Probe Based on Polythiophene Derivative for Pre- and Intraoperative Mapping of Lymph Nodes by SPECT/Optical Imaging

The metastatic spread of primary tumors to regional lymph nodes (LNs) is an important prognostic indicator for cancer staging and clinical therapy. Therefore, developing lymphatic mapping probes with improved accuracy and efficiency is of vital importance. Conjugated polymers (CPs) have been established as useful optical probes for sensitive biological and chemical detection. As a member of CPs family, polythiophene derivatives have drawn increasing attraction because of their superior photostability, signal amplification ability, and flexible structures for modification. In addition, these excellent properties allow the promising in vivo application to real-time LNs mapping. Here, we first reported a radiolabeled dual-modal probe based on the polythiophene derivative (^99mTc-PTP) that was used for LNs mapping with high sensitivity and specificity by preoperative single-photon emission computed tomography imaging and intraoperative optical guidance. ^99mTc-PTP exhibits an excellent radio-fluorescence guidance ability and a remarkable biocompatibility and holds great potential to be a powerful probe for noninvasive LNs mapping

Synthesis and Preliminary Study of ^99mTc-Labeled HYNIC-FAPi for Imaging of Fibroblast Activation Proteins in Tumors

Fibroblast activation protein (FAP) is an emerging target for cancer diagnosis. Different types of FAP inhibitor (FAPI)-based radiotracers have been developed and applied for tumor imaging. However, few FAPI tracers for single photon emission computed tomography (SPECT) imaging have been reported. SPECT imaging is less expensive and more widely distributed than positron emission tomography (PET), and thus, 99mTc-labeled FAPIs would be more available to patients in developing regions. Herein, we developed a FAPI-04-derived radiotracer, HYNIC-FAPi-04 (HFAPi), for SPECT imaging. 99mTc-HFAPi, with a radiochemical purity of >98%, was prepared using a kit formula within 30 min. The specificity of 99mTc-HFAPi for FAP was validated by a cell binding assay in vitro and SPECT/CT imaging in vivo. The binding affinity (Kd value) of 99mTc-HFAPi for human FAP and murine FAP was 4.49 and 2.07 nmol/L, respectively. SPECT/CT imaging in HT1080-hFAP tumor-bearing mice showed the specific FAP targeting ability of 99mTc-HFAPi in vivo. In U87MG tumor-bearing mice, 99mTc-HFAPi had a higher tumor uptake compared with that of HT1080-hFAP and 4T1-mFAP tumor models. Interestingly, 99mTc-HFAPi showed a relatively high uptake in some murine joints. 99mTc-HFAPi accumulated in tumor lesions with a high tumor-to-background ratio. A preliminary clinical study was also performed in breast cancer patients. Additionally, 99mTc-HFAPi exhibited an advantage over 18F-FDG in the detection of lymph node metastatic lesions in breast cancer patients, which is helpful in improving treatment strategies. In short, 99mTc-HFAPi showed excellent affinity and specificity for FAP and is a promising SPECT radiotracer for (re)staging and treatment planning of breast cancers

Comparison of ^99mTc-3PRGD2 Integrin Receptor Imaging with ^99mTc-MDP Bone Scan in Diagnosis of Bone Metastasis in Patients with Lung Cancer: A Multicenter Study

<div><p>Purpose</p><p>^99mTc-3PRGD2, a promising tracer targeting integrin receptor, may serve as a novel tumor-specific agent for single photon emission computed tomography (SPECT). A multi-center study was prospectively designed to evaluate the diagnostic accuracy of ^99mTc-3PRGD2 imaging for bone metastasis in patients with lung cancer in comparison with the conventional ^99mTc-MDP bone scan.</p><p>Methods</p><p>The patients underwent whole-body scan and chest tomography successively at both 1 h and 4 h after intravenous injection of 11.1 MBq/Kg ^99mTc-3PRGD2. ^99mTc-MDP whole-body bone scan was routinely performed within 1 week for comparison. Three experienced nuclear medicine physicians blindly read the ^99mTc-3PRGD2 and ^99mTc-MDP images. The final diagnosis was established based on the comprehensive assessment of all available data.</p><p>Results</p><p>A total of 44 patients (29 male, 59±10 years old) with suspected lung cancer were recruited from 4 centers. Eighty-nine bone lesions in 18 patients were diagnosed as metastases and 23 bone lesions in 9 patients were benign. In a lesion-based analysis, ^99mTc-3PRGD2 imaging demonstrated a sensitivity, specificity, and accuracy of 92.1%, 91.3%, and 92.0%, respectively. The corresponding diagnostic values for ^99mTc-MDP bone scan were 87.6%, 60.9%, and 82.1%, respectively in the same patients. ^99mTc-MDP bone scan had better contrast in most lesions, whereas the ^99mTc-3PRGD2 imaging seemed to be more effective to exclude pseudo-positive lesions and detect bone metastases without osteogenesis.</p><p>Conclusion</p><p>^99mTc-3PRGD2 is a novel tumor-specific agent based on SPECT technology with a promising value in diagnosis of bone metastasis in patients with lung cancer.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01737112?term=NCT01737112&rank=1" target="_blank">NCT01737112</a></p></div

Flowchart of the study.

<p>Flowchart of the study.</p

The recruited patient number and SPECT systems of the 4 centers.

<p>The recruited patient number and SPECT systems of the 4 centers.</p

Comparison of the diagnostic efficacy of ^99mTc-3PRGD2 integrin receptor imaging and ^99mTc-MDP bone scan for bone metastasis.

<p>a:1-h RGD vs. MDP.</p><p>b:4-h RGD vs. MDP.</p><p>c:1-h vs. 4-h RGD.</p><p>PPV: positive predictive value; NPV: negative predictive value; RGD: ^99mTc-3PRGD2 imaging; MDP: ^99mTc-MDP bone scan.</p><p>Comparison of the diagnostic efficacy of ^99mTc-3PRGD2 integrin receptor imaging and ^99mTc-MDP bone scan for bone metastasis.</p

^99mTc-HisoDGR as a Potential SPECT Probe for Orthotopic Glioma Detection via Targeting of Integrin α₅β₁

Integrins, a large family of cell adhesion receptors, have been shown to play an important role for glioma proliferation and invasion. Several integrin receptors, including α_vβ₃, α_vβ₅, and α₅β₁, have generated clinical interest for glioma diagnosis and antitumor therapy. Integrin α₅β₁ has been highlighted as a prognostic and diagnostic marker in glioma, and its expression is correlated with a worse prognosis in high-grade glioma. However, unlike extensively studied integrins α_vβ₃ and α_vβ₅, very few integrin α₅β₁-specific radiotracers have been reported. Developing α₅β₁-specific radiotracers may provide alternative diagnosis and evaluation options in addition to well-studied α_vβ₃/α_vβ₅-specific tracers, and they may add new documents for profiling tumor progression. Here, a novel integrin α₅β₁-specific probe ^99mTc-HisoDGR was fabricated for SPECT (single-photon emission computed tomography) imaging of glioma. To confirm its selective targeting of integrin α₅β₁ in vivo, the mouse models of α₅β₁-positive U87MG human glioma were subjected to SPECT/CT scans, and biodistribution experiments and blocking studies were performed. Small-animal SPECT/CT imaging experiments demonstrated that the tumors were clearly visualized in both subcutaneous and orthotopic glioma tumor models with clear background at 0.5, 1, and 2 h p.i. The tumor accumulation of ^99mTc-HisoDGR showed significant reduction when excess cold isoDGR peptide was coinjected, suggesting that the tumor uptake was specifically mediated. Our work revealed that ^99mTc-HisoDGR represented a powerful molecular probe for integrin α₅β₁-positive cancer imaging; moreover, it might be a promising tool for evaluating malignancy, predicting prognosis, selecting subpopulations of patients who might be sensitive to integrin α₅β₁-targeted drugs, and assessing and monitoring the response to integrin α₅β₁-targeted drugs in clinical trials

Nonaqueous System of Iron-Based Ionic Liquid and DMF for the Oxidation of Hydrogen Sulfide and Regeneration by Electrolysis

To improve the hydrogen sulfide removal efficiency with the application of an iron-based imidazolium chloride ionic liquid (Fe­(III)-IL) as desulfurizer, Fe­(II) and <i>N</i>,<i>N</i>-dimethylformamide (DMF) are introduced to Fe­(III)-IL to construct a new nonaqueous desulfurization system (Fe­(III/II)-IL/DMF). Following desulfurization, the system can be regenerated using the controlled-potential electrolysis method. The addition of Fe­(II) in Fe­(III)-IL is beneficial for the hydrogen sulfide removal and the electrochemical regeneration of the desulfurizer. The addition of DMF in Fe­(III/II)-IL does not change the structure of Fe­(III/II)-IL but clearly decreases the acidity, increases the electrolytic current, and decreases the stability of the Fe–Cl bond in Fe­(III/II)-IL. Fe­(III/II)-IL/DMF can remove hydrogen sulfide and can be regenerated through an electrochemical method more efficiently than can Fe­(III/II)-IL. After six cycles, the desulfurization efficiency remains higher than 98%, and the average conversion rate of Fe­(II) is essentially unchanged. No sulfur peroxidation occurs, and the system remains stable. Therefore, this new nonaqueous system has considerable potential for removing H₂S in pollution control applications

Comparison of ^99mTc-3PRGD2 SPECT, ^99mTc-MDP bone scan (posterior), and CT scan in a 62 year-old woman with left upper lung adenocarcinoma (green arrow) and costal metastasis (red arrow).

<p>A:^99mTc -3PRGD2 WB(+), B: ^99mTc -3PRGD2 SPECT (+), C: ^99mTc -MDP bone scan (+), D: CT (+). WB: whole body.</p

Comparison of ^99mTc-3PRGD2 SPECT, ^99mTc -MDP bone scan, and ¹⁸F-FDG PET in a 60 year-old patient with a recent fall-down trauma.

<p>The^99mTc -MDP bone scan was positive (red arrows), whereas both ^99mTc-3PRGD2 SPECT and ¹⁸F-FDG PET were negative. A: ^99mTc-3PRGD2 WB (-), B: ^99mTc-3PRGD2 SPECT (−), C: ^99mTc-MDP bone scan (+), D: ¹⁸F-FDG PET (−). WB: whole body.</p