⁶⁸Ga-NOTA-Aca-BBN(7–14) PET/CT in Healthy Volunteers and Glioma Patients

Abstract

This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)– targeting, 68Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7–14) (denoted as 68Ga-BBN) in healthy volunteers and to assess the level of receptor expression in glioma patients. Methods Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of 68Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time–activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30–45 min after 68Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. Results 68Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. 68Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In glioma patients, all MRI-identified lesions showed high signal intensity on 68Ga-BBN PET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r2 = 0.71, P < 0.001). Conclusion 68Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in glioma patients and guide GRPR-targeted therapy of glioma.

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

“…Integrin a v b 3 activation on tumor cells is essential for the recognition of key bone-specific matrix proteins, suggesting that the a v b 3 integrin modulates prostate cancer growth in distant metastasis (33). In a recently published clinical study in prostate cancer patients using 18 F-galacto-RGD PET, 58 of 74 bone lesions were identified, with a detection rate of 78.4% (34). Thus, RGD moiety in 68 Ga-BBN-RGD may play a major role in bone metastasis detection.…”

“…For the volunteers, the dosimetry calculation was performed according to the EANM Dosimetry Guidance (25) and calculated using OLINDA/ EXM (version 1.1; Vanderbilt University) with the procedure reported in a previous study (18). The void time of the bladder was set as 60 min.…”

“…The radiochemical purity of the product 68 Ga-BBN-RGD exceeded 97%. 68 Ga-BBN was synthesized following a procedure reported previously (18).…”

“…Several bombesin-related tracers have also been translated into the clinic for early phase studies (13)(14)(15)(16)(17). Previously, we have applied the GRPR-specific PET tracer 68 Ga-NOTA-Aca-BBN (7)(8)(9)(10)(11)(12)(13)(14) (denoted as 68 Ga-BBN) for first-in-human studies in both healthy volunteers and patients with both low-and high-grade gliomas (18).…”

“…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).…”