Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy

Ma, Qingjie; Ji, Bin; Jia, Bing; Gao, Shi; Ji, Tiefeng; Wang, Xueju; Han, Zhenguo; Zhao, Guoqing

doi:10.1007/s00259-011-1901-2

Cited by 54 publications

(54 citation statements)

References 22 publications

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“…Synthesis of the labeling precursor, kit preparation, and subsequent 99m Tc-labeling were performed as previously described (21,22). Briefly, the kit for preparation of 99m Tc-3PRGD2 was formulated by combining 20 mg of hydrazinonicotinamide-3PRGD2, 5 mg of trisodium triphenylphosphine-3,39,399-trisulfonate (TPPTS), 6.5 mg of tricine, 40 mg of mannitol, 38.5 mg of disodium succinate hexahydrate, and 12.7 mg of succinic acid.…”

Section: Radiopharmaceutical Preparationmentioning

confidence: 99%

“…As a representative, 99m Tc-3PRGD2 could be easily prepared in a kit formulation and exhibited excellent in vivo behaviors in nonhuman primates (21). Recently, it was used in patients and appeared useful for differentiation of solitary pulmonary nodules (22). 99m Tc-3PRGD2 is mainly excreted by the kidneys.…”

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confidence: 99%

“…It has a rapid blood clearance, with less than 1% of the initial radioactivity remaining in the blood circulation at 60 min after injection (21). No adverse reactions are observed in animal models and humans to date (18)(19)(20)(21)(22).…”

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^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

Zhu

Miao²,

Li³

et al. 2012

J Nucl Med

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116

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99m Tc-3PRGD2 is a new SPECT tracer targeting integrin a V b 3 receptor for detecting tumors, imaging angiogenesis, and evaluating tumor response to therapy. A multicenter study was designed to investigate the efficacy of 99m Tc-3PRGD2 for the evaluation of patients with lung cancer. Methods: Seventy patients (51 men, 19 women; mean age 6 SD, 63 6 9 y) with a suspected lung lesion and for whom definite pathologic diagnosis was finally obtained (malignant, n 5 58; benign, n 5 12) were recruited from 6 centers. Whole-body planar scanning and chest SPECT were performed at 1 and 4 h, respectively, after intravenous injection of 11.1 MBq/kg (0.3 mCi/kg) of 99m Tc-3PRGD2. The images were read in consensus by 6 experienced nuclear medicine physicians masked to the source, history, and pathologic diagnosis. The tumor-to-background (T/B) ratios were calculated for semiquantitative analysis. A Student t test was used for statistical analysis, and a P value less than 0.05 was considered significant. Results: With low 99m Tc-3PRGD2 background in the lungs and mediastinum, most lung malignancies were prominent on the 1-h images (T/B ratio, 1.65 6 0.47 for the planar imaging and 2.78 6 1.52 for SPECT). The T/B ratios were significantly lower in the benign lesions (P , 0.05). The sensitivity was 88% for semiquantitative analysis and could reach 93%-97% in visual analysis when considering the volume effect, necrosis, and metastasis. However, the specificity was only 58%-67%. Most lymph node and bone metastases could also be detected. Conclusion: 99m Tc-3PRGD2 imaging at 1 h is sensitive for the detection of lung cancer, meriting further investigation of 99m Tc-3PRGD2 as a novel clinical tracer for integrin receptor imaging. Si nce integrins were revealed as an important family of transmembrane receptors about 30 y ago, they have been widely studied and are found to play essential roles in angiogenesis and tumor metastasis because they are mainly involved in the cell-cell and cell-matrix interactions (1). Integrin a V b 3 is an important member of this receptor family and expressed preferentially on various types of tumor cells and the activated endothelial cells of tumor angiogenesis but not at all or very little on the quiescent vessel cells and other normal cells (2,3). Therefore, the integrin a V b 3 receptor is becoming a valuable target for diagnosis and treatment of malignant tumors (4,5).The tripeptide sequence of arginine-glycine-aspartic acid (RGD) can specifically bind to the integrin a V b 3 receptor (6,7). Accordingly, a variety of radiolabeled RGD-based peptides have been developed for noninvasive imaging of integrin a v b 3 expression via PET or . Among all the RGD radiotracers studied, 2 PET agents, 18 F-galacto-RGD and 18 F-AH111585, have been well investigated in clinical trials. The results demonstrated that both radiotracers allowed the specific imaging of various types of tumors, and the tumor uptake correlated well with the expression of integrin a v b 3 in both animal models and patients (9-14). The 99m Tc...

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Section: Radiopharmaceutical Preparationmentioning

confidence: 99%

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confidence: 99%

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^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

Zhu

Miao²,

Li³

et al. 2012

J Nucl Med

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116

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“…Additionally, detailed biodistribution and measured radiation dosimetry in humans have been reported for 18 F-galactoRGD (26), 18 F-RGD-K5 (27), 68 Ga-NOTA-RGD (28), and 18 F-FPPRGD2 (29). Given the proven higher affinity of RGDdimeric conjugates for a V b 3 integrin receptors (17)(18)(19)(20), RGDdimeric derivatives labeled with 99m Tc (30,31) for SPECT and with 18 F (29,32) for PET have been evaluated in humans.…”

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confidence: 99%

PET-Based Human Dosimetry of the Dimeric α_vβ₃ Integrin Ligand ⁶⁸Ga-DOTA-E-[c(RGDfK)]₂, a Potential Tracer for Imaging Tumor Angiogenesis

et al. 2015

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Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for α v β 3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from 68 Ga-DOTA-E-[c(RGDfK)] 2 using whole-body PET scans in humans. Methods: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/ EXM software was applied to calculate human radiation doses using the reference adult model. Results: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively. Conclusion: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with 68 Ga and 18 F. Therefore, 68 Ga-DOTA-E-[c(RGDfK)] 2 can safely be used for imaging integrin α V β 3 expression. The last few years have witnessed the development of a virtual revolution in PET molecular imaging, and radiolabeled receptor-binding peptides are emerging as powerful tools for imaging and therapy applications of tumors expressing peptide binding receptors (1-3). Somatostatin analogs have been in use the longest, have led to the accumulation of a vast amount of data, and have proven useful for the management of patients with neuroendocrine tumors (4-8). Several other peptide receptorbinding compounds have been synthesized within the past few years and are currently in various research stages-in vitro, in vivo, and preclinical studies-but have not yet been approved for clinical use (9-11). These new and rapidly expanding peptide-based radiopharmaceuticals deserve close attention.It has been shown that peptides based on the RGD amino acid sequence have a high affinity and selectivity for a V b 3 integrin receptors (12). The a V b 3 integrins are transmembrane proteins that are preferentially expressed on proliferating endothelial cells but absent from quiescent endothelial cells (13). Integrins are overexpressed on newly formed blood vessels of actively growing tumors and are therefore potential targets for receptor-mediated tumor imaging and therapy when labeled with the proper radionuclide. Angiogenesis, the formation of n...

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“…Immunohistochemistry of GRPR and α v β 3 Expression GRPR and a v b 3 expression was analyzed by immunohistochemistry, as described previously with some modifications (16,17). The abnormal tissues were snap-frozen, sectioned (3 mm), fixed with ice-cold acetone, rinsed with phosphate-buffered saline, and blocked with 10% goat serum for 30 min at room temperature.…”

Section: Subjectsmentioning

confidence: 99%

^99mTc-Glu-c(RGDyK)-Bombesin SPECT Can Reduce Unnecessary Biopsy of Masses That Are BI-RADS Category 4 on Ultrasonography

Gao

Liu

et al. 2016

J Nucl Med

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Masses that, on ultrasonography, are category 4 according to the Breast Imaging Reporting and Data System (BI-RADS) represent possible malignancy, and a biopsy is recommended. This study explored the value of 99m Tc-Glu-c(RGDyK)-bombesin ( 99m Tc-RGD-bombesin) in reducing unnecessary biopsy of these masses. Methods: Ninety women with a BI-RADS 4 mass on ultrasonography were enrolled in this study to undergo breast SPECT using 99m Tc-RGD-bombesin. The images were independently interpreted using qualitative visual and semiquantitative analyses. The final diagnosis was based on histopathologic examination of surgically excised or percutaneous biopsy specimens. Fractions of the samples were immunohistochemically analyzed to evaluate expression of integrin α v β 3 and gastrinreleasing peptide receptor (GRPR). The receptor-positive group was further divided into 3 subgroups (GRPR 1 /α v β 3 1 , GRPR 1 /α v β 3 − , and α v β 3 1 /GRPR − ). Results: Ninety-four masses (22 malignant and 72 benign) were confirmed by histopathologic examination. On qualitative analysis, 20 of the malignant masses showed high 99m Tc-RGDbombesin accumulation and 48 of the benign masses showed no 99m Tc-RGD-bombesin accumulation. The optimal cutoff for qualitative analysis was a score of 2. Semiquantitative analysis revealed that 20 of the malignant masses and 16 of the benign masses had a relatively high tumor-to-normal-tissue ratio (T/N). The optimal cutoff was a T/N of 2.26. The mean T/N was higher for malignant masses than for benign masses (3.17 ± 0.86 vs. 1.89 ± 0.71, P , 0.05). T/Ns did not differ among the 3 subgroups (P . 0.05). The areas under the receiver-operating-characteristic curves for the qualitative and semiquantitative analyses were 0.788 and 0.865, respectively, and the overall diagnostic performance did not significantly differ between these analyses (P . 0.05). Conclusion: 99m Tc-RGD-bombesin SPECT can differentiate benign from malignant BI-RADS 4 masses with high specificity. Further study of the application of this test to clinical breast cancer appears warranted.

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Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy

Abstract: In this first-in-human study, we demonstrated the feasibility of using (99m)Tc-3P(4)-RGD(2) scintigraphy in differentiating SPNs. This procedure appears to be highly sensitive in detection of malignant SPNs. SPECT visual analysis seems to be sufficient for characterization of SPNs.

Cited by 54 publications

References 22 publications

^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

PET-Based Human Dosimetry of the Dimeric α_vβ₃ Integrin Ligand ⁶⁸Ga-DOTA-E-[c(RGDfK)]₂, a Potential Tracer for Imaging Tumor Angiogenesis

^99mTc-Glu-c(RGDyK)-Bombesin SPECT Can Reduce Unnecessary Biopsy of Masses That Are BI-RADS Category 4 on Ultrasonography

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Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2 scintigraphy

Abstract: In this first-in-human study, we demonstrated the feasibility of using (99m)Tc-3P(4)-RGD(2) scintigraphy in differentiating SPNs. This procedure appears to be highly sensitive in detection of malignant SPNs. SPECT visual analysis seems to be sufficient for characterization of SPNs.

Cited by 54 publications

References 22 publications

99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

PET-Based Human Dosimetry of the Dimeric αvβ3 Integrin Ligand 68Ga-DOTA-E-[c(RGDfK)]2, a Potential Tracer for Imaging Tumor Angiogenesis

99mTc-Glu-c(RGDyK)-Bombesin SPECT Can Reduce Unnecessary Biopsy of Masses That Are BI-RADS Category 4 on Ultrasonography

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^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

^99mTc-3PRGD2 for Integrin Receptor Imaging of Lung Cancer: A Multicenter Study

PET-Based Human Dosimetry of the Dimeric α_vβ₃ Integrin Ligand ⁶⁸Ga-DOTA-E-[c(RGDfK)]₂, a Potential Tracer for Imaging Tumor Angiogenesis

^99mTc-Glu-c(RGDyK)-Bombesin SPECT Can Reduce Unnecessary Biopsy of Masses That Are BI-RADS Category 4 on Ultrasonography