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

Abstract

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.

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

“…In particular, they can be targeted by bombesin (i.e., a 14-AA peptide with the sequence pEQRLGNQWAVGHLM-NH 2 ) or arginine-glycine-aspartic acid (RGD) derivatives. 79,80 Consequently, in 2008, van Lier and co-workers were the first to synthesize a bombesin-Pc conjugate to target the GRP receptor. 54 To this end, they made use of tetrasulphonated Al(III)Pc (AlPcS 4 ), observing that the photodynamic efficacy in PC-3 human prostate cancer cells had improved with conjugation.…”

Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

“…2 and Table 1). This fact could be explained based on the concentration of unlabeled peptides Affinity, cell uptake, and viability assays indicated that 177 Lu-iPSMA-RGD was not able to concomitantly recognize two receptors on the cell surface or to improve the cell uptake concerning 177 Lu-iPSMA or 177 Lu-RGD monomers, as other authors have reported for heterobivalent molecules [11][12][13]. However, the intrinsic heterogenicity of human tumors, as well as changes in phenotype during disease progression, including the different level expression of cell surface receptors, is well-known.…”

“…The research on new heterobivalent radiopharmaceuticals that interact with two different targets on tumor cells is a strategy for the enhancement of tumor imaging and therapy [11][12][13]. Therefore, a heterobivalent conjugate of iPSMA and RGD is expected to improve the recognition of cancer cells positive for PSMA and a(v)b (3) integrins.…”

Emerging Perspectives on Applications of Porphyrinoids for Photodynamic Therapy and Photoinactivation of Microorganisms

“…On the other hand, GRP and α v β 3 integrin are proteins that are expressed in different tumours, being a receptor of a peptide called bombesin in the first case, and of a peptide called RGD triad or arginylglycylaspartic acid in the second case. [17,25] Van Lier et al have developed different Zn(II) Pc-bombesin and Zn(II)Pc-RGD conjugates. [26] These bioconjugates were evaluated in cell lines that express GRP and integrin receptors and the results showed that the first one, a Zn(II)Pc-bombes in biohybrid, expressed a good aqueous solubility and was a potential candidate for being used as fluorescence imaging probe and photodynamic agent.…”