JEAS  Vol.10 No.2 , June 2020
Synthesis and Radiation Dosimetry of [68Ga]-Ga-Lys1, Lys3-DOTA-Bombesin (1,14) Antagonist for PET-Imaging, as a Potential Theragnostic Tracer in Oncology
Abstract: This Bombesin (BBN), a tetradecapeptide analog of human gastrin-releasing peptide (GRP) with a high binding affinity for GRP receptors (GRPR), is over- expressed in early stages of androgen-dependent prostate carcinomas, but not in advanced stages. Therefore, there is a need to develop effective tracers for the accurate and specific detection of this disease. The objective of this study was to evaluate Lys1, Lys3-DOTA-BBN (1,14) analog with the radiolabeled positron emitter [68Ga]-Ga-BBN for receptor imaging with PET, and to determine its biodistribution and radiation dosimetry using whole-body (WB) PET scans in healthy volunteers. The highest uptake was in the pancreas, followed by urinary bladder. The critical organ was pancreas with a mean absorbed dose of 206 ± 0.7, 210 ± 0.7, 120 ± 0.9, 390.23 ± 0.6 μGy/MBq and the effective doses were estimated as 73.2 ± 0.6, 49.8 ± 0.3 μGy/MBq (women and men, respectively).
Cite this paper: Manrique-Arias, J. , Pitalua-Cortes, Q. , Pedrero-Piedras, R. , Rodríguez-Mena, G. , López, T. , Cabezas-Ortiz, C. and García-Pérez, O. (2020) Synthesis and Radiation Dosimetry of [68Ga]-Ga-Lys1, Lys3-DOTA-Bombesin (1,14) Antagonist for PET-Imaging, as a Potential Theragnostic Tracer in Oncology. Journal of Encapsulation and Adsorption Sciences, 10, 29-41. doi: 10.4236/jeas.2020.102002.

[1]   Malik, A.S., Boyko, O., Atkar, N. and Young, W.F. (2001) A Comparative Study of MR Imaging Profile of Titanium Pedicle Screws. Acta Radiologica, 42, 291-293.

[2]   Ferlay, J., Shin, H.R., Bray, F., Forman, D., Mathers, C. and Parkin, D.M. (2010) Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008. International Journal of Cancer, 127, 2893-2917.

[3]   Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A. and Jemal, A. (2018). Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424.

[4]   Cescato, R., Maina, T., Nock, B., et al. (2008) Bombesin Receptor Antagonist May Be Preferable to Agonist for Tumor Targeting. Journal of Nuclear Medicine, 49, 318-326.

[5]   Ferro-Flores, G., de Murphy, C.A., Rodriguez-Cortes, J., et al. (2006) Preparation and Evaluation of 99mTc-EDDA/HYNIC-[Lys3]-Bombesin for Imaging Gastrin-Re- leasing Peptide Receptor-Positive Tumours. Nuclear Medicine Communications, 27, 371-376.

[6]   Wu stemann, T., Bauder-Wu st, U., Scha fer, M., et al. (2016) Design of Internalizing PSMA-Specific Gluureido-Based Radiotherapeuticals. Theranostics, 6, 1085-1095.

[7]   Ray Banerjee, S., Chen, Z., Pullambhatla, M., et al. (2016) Preclinical Comparative Study of 68Ga-Labeled DOTA, NOTA, and HBED-CC Chelated Radiotracers for Targeting PSMA. Bioconjugate Chemistry, 27, 1447-1455.

[8]   Saatchi, K., Gelder, N., Gershkovich, P., Sivak, O., Wasan, K.M., Kainthan, R.K., Brooks, D.E. and Häfeli U.O. (2012) Long-Circulating Non-Toxic Blood Pool Imaging Agent Based on Hyperbranched Polyglycerols. International Journal of Phar- maceutics, 422, 418-427.

[9]   Reubi, J.C., Körner, M., Waser, B., Mazzucchelli, L. and Guillou, L. (2004) High Expression of Peptide Receptors as a Novel Target in Gastrointestinal Stromal Tumours. European Journal of Nuclear Medicine and Molecular Imaging, 31, 803-810.

[10]   Yang, M., Gao, H., Zhou, Y., et al. (2011) 18F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging. Theranostics, 1, 220-229.

[11]   Alejandro, A.C., Megan, S., Marian, M., Shankar, V. and John W., B. (2016) Comprehensive Quality Control of the ITG 68Ge/68Ga Generator and Synthesis of 68Ga- DOTATOC and 68Ga-PSMA-HBED-CC for Clinical Imaging. The Journal Nuclear Medicine, 57, 1402-1405.

[12]   Stabin, M.G. and Siegel, J.A. (2003) Physical Models and Dose Factor for Use in Internal Dose Assessment. Health Physics, 85, 294-310.

[13]   Stabin, M.G., Sparks, R.B. and Crowe, E. (2005) OLINDA/EXM: The Second-Gene- ration Personal Computer Software for Internal Dose Assessment in Nuclear Medicine. Journal of Nuclear Medicine, 46, 1023-1027.

[14]   Siegel, J.A., Thomas, S.R., Stubbs, J.B., et al. (1999) MIRD Pamphlet No. 16: Techniques for Quantitative Radiopharmaceutical Biodistribution Data Acquisition and Analysis for Use in Human Radiation Dose Estimates. Journal of Nuclear Medicine, 40, 37S-61S.

[15]   International Commission on Radiological Protection (ICRP) (1991) 1990 Recommendations of the International Commission of Radiological Protection. ICRP Publication 60. Pergamon Press, New York.

[16]   Fleischmann, A., Waser, B. and Reubi, J.C. (2007) Overexpression of Gastrin-Re- leasing Peptide Receptors in Tumor-Associated Blood Vessels of Human Ovarian Neoplasms. Cellular Oncology, 29, 421-433.

[17]   Sharif, T.R., Luo, W. and Sharif, M. (1997) Functional Expression of Bombesin Receptor in Most Adult and Pediatric Human Glioblastoma Cell Lines: Role in Mitogenesis and in Stimulating the Mitogen-Activated Protein Kinase Pathway. Molecular and Cellular Endocrinology, 130, 119-130.

[18]   Chen, X., Park, R., Hou, Y., et al. (2004) microPET and Autoradiographic Imaging of GRP Receptor Expression with 64Cu-DOTA-[Lys3] Bombesin in Human Prostate Adenocarcinoma Xenografts. Journal of Nuclear Medicine, 45, 1390-1397.

[19]   Zhang, X., Cai, W., Cao, F., et al. (2006) 18F-Labeled Bombesin Analogs for Targeting GRP Receptor-Expressing Prostate Cancer. Journal of Nuclear Medicine, 47, 492-501.

[20]   Smith, C.J., Volkert, W.A. and Hoffman, T.J. (2005) Radiolabeled Peptide Conjugates for Targeting of the Bombesin Receptor Superfamily Subtypes. Nuclear Medicine and Biology, 32, 733-740.

[21]   Prasanphanich, A.F., Nanda, P.K., Rold, T.L., et al. (2007) [64Cu-NOTA-8-Aoc- BBN-(7-14) NH2] Targeting Vector for Positron-Emission Tomography Imaging of Gastrin-Releasing Peptide Receptor-Expressing Tissues. Proceedings of the National Academy of Sciences of the United States of America, 104, 12462-12467.

[22]   Liu, Z., Niu, G., Wang, F. and Chen, X. (2009) 68Ga-Labeled NOTA-RGD-BBN Peptide for Dual Integrin and GRPR-Targeted Tumor Imaging. European Journal of Nuclear Medicine and Molecular Imaging, 36, 1483-1494.

[23]   Gonzalez, N., Moody, T.W., Igarashi, H., Ito, T. and Jensen, R.T. (2008) Bombesin-Related Peptides and Their Receptors: Recent Advances in Their Role in Physiology and Disease States. Current Opinion in Endocrinology, Diabetes and Obesity, 15, 58-64.

[24]   Strauss, L.G., Koczan, D., Seiz, M., et al. (2012) Correlation of the Ga-68-Bombesin analog Ga-68-BZH3 with Receptors Expression in Gliomas as Measured by Quantitative Dynamic Positron Emission Tomography (dPET) and Gene Arrays. Molecular Imaging and Biology, 14, 376-383.

[25]   Mansi, R., Minamimoto, R., Mäcke, H., et al. (2016) Bombesin-Targeted PET of Prostate Cancer. The Journal of Nuclear Medicine, 57, 67S-72S.

[26]   Schroeder, R.P.J., de Visser, M., van Weerden, W.M., de Ridder, C.M.A., Reneman, S., Melis, M., Breeman, W.A.P., Krenning, E.P. and de Jong, M. (2010) Androgen-Regulated Gastrin-Releasing Peptide Receptor Expression in Androgen-Depen- dent Human Prostate Tumor Xenografts. International Journal of Cancer, 126, 2826- 2834.

[27]   Ramos-álvarez, I., Moreno, P., Mantey, S.A., Nakamura, T., Nuche-Berenguer, B., Moody, T.W., Coy, D.H. and Jensen, R.T. (2015) Insights into Bombesin Receptors and Ligands: Highlighting Recent Advances. Peptides, 72, 128-144.