<sup>18</sup>F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging

Li, Zibo; Wu, Zhanhong; Chen, Kai; Ryu, Eung K.; Chen, Xiaoyuan

doi:10.2967/jnumed.107.048009

Cited by 133 publications

(148 citation statements)

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“…One major advantage of heterodimer over the corresponding monomers is the multivalency effect, resulting in improved binding affinity and increased number of effective receptors (20,(22)(23)(24). Consistently, both 68 Ga-BBN-RGD and 68 Ga-BBN showed uptake in the primary prostate tumors that were either GPRR-positive or integrin a v b 3 -positive.…”

Section: Discussionsupporting

confidence: 52%

“…Within this heterodimer, the RGD moiety binds to integrin a v b 3 receptor, which plays an important role in the regulation of tumor growth, angiogenesis, local invasiveness, and metastatic potential (21). In a PC3 xenograft model, 18 F-FB-BBN-RGD had significantly higher tumor uptake than monomeric RGD and monomeric BBN peptide tracer analogs at all time points examined (20). A series of preclinical studies using the same strategy have confirmed several advantages of heterodimers including increased number of effective receptors, improved binding affinity, and pharmacokinetics (20,(22)(23)(24).…”

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confidence: 98%

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Clinical Translation of a Dual Integrin α_vβ₃– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, ⁶⁸Ga-BBN-RGD

et al. 2016

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This study aimed to document the first-in-human application of a 68 Ga-labeled heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin a v b 3 and gastrin-releasing peptide receptor (GRPR). We evaluated the safety and assessed the clinical diagnostic value of 68 Ga-BBN-RGD PET/CT in prostate cancer patients in comparison with 68 Ga-BBN. Methods: Five healthy volunteers (4 men and 1 woman; age range, 28-53 y) were enrolled to validate the safety of 68 Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software. Thirteen patients with prostate cancer (4 newly diagnosed and 9 posttherapy) were enrolled. All the patients underwent PET/CT scans 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68 Ga-BBN-RGD and also accepted 68 Ga-BBN PET/CT within 2 wk for comparison. Results: With a mean injected dose of 107.3 6 14.8 MBq per patient, no side effect was found during the whole procedure and 2 wk follow-up, demonstrating the safety of 68 Ga-BBN-RGD. A patient would be exposed to a radiation dose of 2.90 mSv with an injected dose of 129.5 MBq (3.5 mCi), which is much lower than the dose limit set by the Food and Drug Administration. In 13 patients with prostate cancer diagnosed by biopsy, 68 Ga-BBN-RGD PET/CT detected 3 of 4 primary tumors, 14 metastatic lymph nodes, and 20 bone lesions with an SUV max of 4.46 6 0.50, 6.26 6 2.95, and 4.84 6 1.57, respectively. Only 2 of 4 primary tumors, 5 lymph nodes, and 12 bone lesions were positive on 68 Ga-BBN PET/CT, with the SUV max of 2.98 6 1.24, 4.17 6 1.89, and 3.61 6 1.85, respectively. Conclusion: This study indicates the safety and efficiency of a new type of dual integrin a v b 3 -and GRPR-targeting PET radiotracer in prostate cancer diagnosis and staging.

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confidence: 52%

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Clinical Translation of a Dual Integrin α_vβ₃– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, ⁶⁸Ga-BBN-RGD

et al. 2016

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“…A recent study has shown that the a v b 3 integrin promotes bone gain mediated by prostate cancer cells that metastatize to the bone and point to a v b 3 as a potential therapeutic target to block prostate cancer osteoblastic lesions (Keller & Brown 2004, McCabe et al 2007. Besides therapeutic applications, other uses of integrin inhibitors are in the area of imaging and specific delivery of a drug to cancer cells (Chen et al 2001, Moschos et al 2007, Li et al 2008.…”

Section: Discussionmentioning

confidence: 99%

Integrins in prostate cancer progression

Goel¹,

Li²,

Kogan³

et al. 2008

Endocrine Related Cancer

155

184

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Integrins, which are transmembrane receptors for extracellular matrix proteins, play a key role in cell survival, proliferation, migration, gene expression, and activation of growth factor receptors. Their functions and expression are deregulated in several types of cancer, including prostate cancer. In this article, we review the role of integrins in prostate cancer progression and their potential as therapeutic targets.

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“…Potent 99m Tc-based (demobesin-1) and 111 In-based (RM-1) bombesin analogs that were designed for GRPr-based targeting and tested in the PC-3 xenograft model showed high absolute tumor uptake in animals (13,14). Few publications have reported on 18 F labeling of bombesin peptides (15)(16)(17)(18)(19). Our previous study indicated that the negatively charged bombesin derivative 3-cyano-4-18 F-fluoro-benzoyl-Ala(SO 3 H)-Ava-Gln-TrpAla-Val-NMeGly-His-Sta-Leu-NH 2 had much higher prostate tumor uptake than the corresponding positively charged analog (3-cyano-4-18 F-fluoro-benzoyl-Arg-Ava-Gln-Trp-AlaVal-NMeGly-His-Sta-Leu-NH 2 ) (20).…”

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¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

Honer¹,

Mu²,

Stellfeld³

et al. 2011

J Nucl Med

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Bombesin is a peptide exhibiting high affinity for the gastrinreleasing peptide receptor (GRPr), which is highly overexpressed on prostate cancer cells. In the present study, we developed an 18 F-labeled bombesin analog, 18 F-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer. Methods: In vitro pharmacologic studies were performed to characterize the nonradioactive ( 19 F) standard of the bombesin analog for binding affinity and selectivity for GRPr. The stability of 18 F-BAY 86-4367 was determined in murine and human plasma. In vivo, the tumor-targeting potential and pharmacokinetic profile of the 18 F tracer were analyzed with biodistribution experiments and PET studies of prostate tumor-bearing mice. Results: The nonradioactive ( 19 F) standard of the bombesin analog showed subnanomolar and GRPr-selective binding affinity. The stability of the tracer in murine and human plasma was found to be high. In 2 prostate cancer xenograft models (PC-3 and LNCaP), 18 F-BAY 86-4367 showed more specific and effective GRPr-based targeting in vivo than the benchmark radiotracers 18 F-fluoroethylcholine and 18 F-FDG. In addition, rapid tumor targeting and fast renal excretion (;70%) and hepatobiliary excretion (;10%) were identified in both xenograft models. Furthermore, PET studies provided clear and specific visualization of PC-3 tumors in mice. Conclusion: Favorable preclinical data showing specific and effective tumor targeting by 18 F-BAY 86-4367 suggest that a clinical trial be undertaken to test its diagnostic utility in PET for prostate carcinoma patients.

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¹⁸F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging

Cited by 133 publications

References 23 publications

Clinical Translation of a Dual Integrin α_vβ₃– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, ⁶⁸Ga-BBN-RGD

Clinical Translation of a Dual Integrin α_vβ₃– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, ⁶⁸Ga-BBN-RGD

Integrins in prostate cancer progression

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

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18F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging

Cited by 133 publications

References 23 publications

Clinical Translation of a Dual Integrin αvβ3– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, 68Ga-BBN-RGD

Clinical Translation of a Dual Integrin αvβ3– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, 68Ga-BBN-RGD

Integrins in prostate cancer progression

18F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors

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¹⁸F-Labeled BBN-RGD Heterodimer for Prostate Cancer Imaging

Clinical Translation of a Dual Integrin α_vβ₃– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, ⁶⁸Ga-BBN-RGD

Clinical Translation of a Dual Integrin α_vβ₃– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, ⁶⁸Ga-BBN-RGD

¹⁸F-Labeled Bombesin Analog for Specific and Effective Targeting of Prostate Tumors Expressing Gastrin-Releasing Peptide Receptors