An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the αvβ3-selective angiogenesis imaging agent 99mtc-nc100692

Axelsson, Rimma; Bach‐Gansmo, Tore; Castell-Conesa, Joan; McParland, Brian J.

doi:10.3109/02841850903273974

Cited by 54 publications

(39 citation statements)

References 11 publications

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“…Given that integrins play important roles in cell attachment, survival, migration, invasion and angiogenesis 17,[51][52][53] , which are all critical for carcinogenesis, they have attracted considerable attention as potential anticancer targets. Usually anti-integrins are used in combination with other anti-cancer agents but they also have potential as imaging agents in cancer diagnosis [54][55] .…”

Section: Integrins and Diseasementioning

confidence: 99%

Integrins as therapeutic targets: lessons and opportunities

Cox

Brennan

Moran

2010

Nat Rev Drug Discov

413

350

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Section: Integrins and Diseasementioning

confidence: 99%

Integrins as therapeutic targets: lessons and opportunities

Cox

Brennan

Moran

2010

Nat Rev Drug Discov

413

350

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“…Accordingly, a variety of radiolabeled RGD-based peptides have been developed for noninvasive imaging of integrin a v b 3 expression via PET or SPECT (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Among all the RGD radiotracers studied, 2 PET agents, 18 F-galacto-RGD and 18 F-AH111585, have been well investigated in clinical trials.…”

mentioning

confidence: 99%

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

Zhu

Miao²,

Li³

et al. 2012

J Nucl Med

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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“…The RGD molecules 99m Tc-NC100692, 18 F-P-PRGD2, 18 F-AH111585, and 18 F-galacto-RGD have already been used in the molecular imaging of cancer cell lines, animal models, or clinical cancer patients (including in murine osteosarcoma, human colon and renal adenocarcinoma, rat pancreatic tumors, ovarian carcinoma, human breast carcinoma, human glioblastoma, and human melanoma) to trace tumor angiogenesis and metastasis with PET or SPECT (8)(9)(10)(11)(12)(13). The integrin a v b 3 expression level on tumor cell membranes correlates well with the RGD radiotracer tumor uptake on scintigraphy imaging (14).…”

mentioning

confidence: 99%

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

Zhao

Jin

et al. 2012

J Nucl Med

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Integrin a v b 3 has been proposed as a potential imaging target for radiolabeled RGD peptides and a molecular marker for the estimation of tumor angiogenesis, yet it has not been applied in differentiated thyroid cancer (DTC) patients with radioactive iodine-refractory (RAIR) lesions. The current study was conducted to assess the potential of integrin a v b 3 imaging in the detection of RAIR DTC lesions using 99m Tc-PEG 4 -E [PEG 4 -c(RGDfK)] 2 ( 99m Tc-3PRGD2), thus providing a feasible antiangiogenetic therapeutic target. Methods: Ten DTC patients (2 men, 8 women; mean age 6 SD, 56.4 6 9.8 y; age range, 42-73 y) with multiple RAIR metastases were recruited; all patients had both elevated thyroglobulin levels (thyroglobulin-positive) and negative 131 I whole-body scan (WBS) results. Clinical data were collected including history, 131 I WBS, contemporary CT, ultrasonography, thyroid-stimulating hormone, thyroglobulin, and antithyroglobulin. One or 2 target lesions were selected on the contemporary CT images using Response Evaluation Criteria in Solid Tumors 1.0 for all patients, 7 of whom were chosen for the calculation of the rates of lesion growth within the 3 mo before the study. WBS at 30 min and regional SPECT for lesions at 1 h were performed after the intravenous injection of 99m Tc-3PRGD2. Two experienced nuclear medicine physicians read the images in a masked fashion. The tumor-to-background ratios were calculated for further analysis. Results: All the target RAIR metastatic lesions were identified as positive on 99m Tc-3PRGD2 SPECT images. There was a significant correlation between the mean tumor-to-background ratios and mean growth rates of target lesions (r 5 0.878, P 5 0.009). Conclusion: The RAIR ( 131 I WBS-negative/thyroglobulin-positive) metastatic lesions can be traced using 99m Tc-3PRGD2 imaging, meaning these lesions are highly neovascularized. 99m Tc-3PRGD2 angiogenesis imaging can be used for the localization and growth evaluation of RAIR lesions, providing a new therapeutic target and a novel imaging modality to monitor the efficacy of certain antiangiogenetic therapy.

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An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the α_vβ₃-selective angiogenesis imaging agent ^99mtc-nc100692

Abstract: Scintigraphy with (99m)Tc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of (99m)Tc-NC100692 is safe and well tolerated.

Cited by 54 publications

References 11 publications

Integrins as therapeutic targets: lessons and opportunities

Integrins as therapeutic targets: lessons and opportunities

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

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2

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An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the αvβ3-selective angiogenesis imaging agent 99mtc-nc100692

Abstract: Scintigraphy with (99m)Tc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of (99m)Tc-NC100692 is safe and well tolerated.

Cited by 54 publications

References 11 publications

Integrins as therapeutic targets: lessons and opportunities

Integrins as therapeutic targets: lessons and opportunities

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

Integrin αvβ3 Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using 99mTc-3PRGD2

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Resources

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An open-label, multicenter, phase 2a study to assess the feasibility of imaging metastases in late-stage cancer patients with the α_vβ₃-selective angiogenesis imaging agent ^99mtc-nc100692

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

Integrin α_vβ₃ Imaging of Radioactive Iodine–Refractory Thyroid Cancer Using ^99mTc-3PRGD2