Development of a radiolabeled β-human chorionic gonadotropin

Open access

Development of a radiolabeled β-human chorionic gonadotropin

β-Human chorionic gonadotropin (β-hCG) was successively labeled with [67Ga]-gallium chloride after conjugation with freshly prepared diethylenetriaminepentaacetic acid dianhydride (ccDTPA). After solid phase purification of the radiolabeled hormone, high performance liquid chromatography showed radiochemical purity higher than 95 % under optimized conditions (specific activity = 22-23 TBq mM-1, labeling efficiency 80 %). Preliminary in vivo studies (ID g-1, %) in male wild-type rats showed marked gonadal uptake of the tracer after 240 minutes in agreement with the biodistribution studies and reported β-hCG receptors. Target to blood ratios were 5.1 and 15.2 after 3 and 24 hours, respectively, while target to muscle ratios were 35 and 40 after 3 and 24 hours, respectively.

K. B. Michels, F. Xue, G. A. Colditz and W. C. Willett, Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study, Arch. Intern. Med. 167 (2007) 814-820; DOI: 10.1001/archinte.167.8.814.

P. V. Prasad, A. Rani, S. K. Chaube and T. G. Shrivastav, Deciphering a conformation-specific epitope of hCG-beta through immunokinetics, J. Immunoass. Immunochem. 30 (2009) 1-17; DOI: 10.1080/15321810802570277.

B. Ashish, P. T. Selvi and G. S. Murthy, Thermodynamics of hCG-monoclonal antibody interaction: an analysis of real time kinetics data obtained using radiolabeled hCG probe, Biochim. Biophys. Acta. 1572 (2002) 31-36; DOI:10.1016/S0304-4165(02)00274-X.

A. K. Mishra, S. D. Mahale and K. S. Iyer, Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its beta-subunit: possible involvement of the disulfide bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) in receptor binding of the hormone, J. Pept. Res. 58 (2001) 17-26; DOI: 10.1034/j.1399-3011.2001.00866.x.

A. T. Fazleabas, K. M. Donnelly, P. A. Mavrogianis and H. G. Verhage, Secretory and morphological changes in the baboon (Papio anubis) uterus and placenta during early pregnancy, Biol. Reprod. 49 (1993) 695-704; DOI: 14393, 35400004834249.0060.

H. E. Carlson, P. Kane, Z. M. Lei, X. Li and C. V. Rao, Presence of luteinizing hormone/human chorionic gonadotropin receptors in male breast tissues, J. Clin. Endocrinol. Metab. 89 (2004) 4119-4123; DOI: 10.1210/jc.2003-031882.

M. Szajnik, E. Nowak-Markwitz, M. J. Szczepański and M. Spaczyński, Assessment of expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LH/hCGR) and hCG protein in ovarian cancer tissues, Ginekol. Pol. 78 (2007) 939-943.

K. Szepeshazi, A. V. Schally and G. Halmos, LH-RH receptors in human colorectal cancers: unexpected molecular targets for experimental therapy, Int. J. Oncol. 30 (2007) 1485-1492.

A. Jankowska, M. Andrusiewicz, J. Grabowski, E. Nowak-Markwitz and J. B. Warchol, Coexpression of human chorionic gonadotropin beta subunit and its receptor in nontrophoblastic gynecological cancer, Int. J. Gynecol. Cancer 18 (2008) 1102-1107; DOI: 10.1111/j.1525-1438.2007.01151.x.

R. K. Iles, Ectopic hCGbeta expression by epithelial cancer: malignant behaviour, metastasis and inhibition of tumor cell apoptosis, Mol. Cell. Endocrinol. 260-262 (2007) 264-270; DOI: 10.1016/j.mce.2006.02.019.

I. Noci, S. Pillozzi, E. Lastraioli, S. Dabizzi, M. Giachi, E. Borrani, J. Wimalasena, G. L. Taddei, G. Scarselli and A. Arcangeli, hLH/hCG-receptor expression correlates with in vitro invasiveness in human primary endometrial cancer, Gynecol. Oncol. 111 (2008) 496-501; DOI: 10.1016/j.ygyno.2008.08.018.

C. Leuschner and W. Hansel, Targeting breast and prostate cancers through their hormone receptors, Biol. Reprod. 73 (2005) 860-865; DOI: 10.1095/biolreprod.105.043471.

C. Leuschner, C. S. Kumar, W. Hansel, W. Soboyejo, J. Zhou and J. Hormes, LHRH-conjugated magnetic iron oxide nanoparticles for detection of breast cancer metastases, Breast Cancer Res. Treat. 99 (2006) 163-176; DOI: 10.1007/s10549-006-9199-7.

G. Gebauer, N. Mueller, T. Fehm, A. Berkholz, E. P. Beck, W. Jaeger and P. Licht, Expression and regulation of luteinizing hormone/human chorionic gonadotropin receptors in ovarian cancer and its correlation to human chorionic gonadotropin-doxorubicin sensitivity, Am. J. Obstet. Gynecol. 190 (2004) 1621-1628; DOI: 10.1016/j.ajog.2004.03.045.

A. R. Jalilian, L. Mirsadeghi and R. Haji-Hosseini, Preparation and biodistribution of [67Ga]-DTPA-rituximab in normal rats, J. Radioanal. Nucl. Chem. 274 (2007) 175-179; DOI: 10.1007/s10967-007-7241-9.

D. J. Hnatowich, W. W. Layne and R. L. Child, Radioactive labeling of antibody: a simple and efficient method, Science 220 (1983) 613-619; DOI: 10.1126/science.6836304.

S. A. Butler, hCG-mass units, molar conversions, and the standardization of biologic units, Fertil. Steril. 80 (2003) 1533-1534; DOI: 10.1016/S0015-0282(03)02223-4.

A. R. Jalilian, P. Rowshanfarzad, K. Shafaii, M. Kamali-Dehghan, J. Moafian, M. Akhlaghi, M. Babai, S. Rajabifar and M. Mirzaii, Development of 111In-DTPA-human polyclonal antibody complex for long-term inflammation/infection detection, Nukleonika 50 (2005) 91-96.

P. G. Righetti, G. Tudor and K. Ek, Isoelectric points and molecular weights of proteins, J. Chromatogr. 220 (1981) 115-194.

A. J. Ziecik, M. M. Kaczmarek, A. Blitek, A. E. Kowalczyk, X. Li and N. A. Rahman, Novel biological and possible applicable roles of LH/hCG receptor, Mol. Cell. Endocrinol. 269 (2007) 51-60; DOI: 10.1016/j.mce.2006.08.016.

R. Jalilian, P. Mehdipour, M. Akhlaghi, H. Yousefnia and K. Shafaii, Evaluation of a [67Ga]-thiosemicarbazone complex as tumor imaging agent, Sci. Pharm. 77 (2009) 343-354; DOI: 10.3797/scipharm.0812-07.

M. M. Coonce, A. C. Rabideau, S. McGee, K. Smith and K. P. Narayan, Role of androgen and gonadotrophins in the development and function of the Sertoli cells and Leydig cells: data from mutant and genetically modified mice, Mol. Cell. Endocrinol. 298 (2009) 33-41; DOI: 10.1016/j.mce.2008.10.016.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information

IMPACT FACTOR 2017: 1.071
5-year IMPACT FACTOR: 1.623

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.362
Source Normalized Impact per Paper (SNIP) 2017: 0.642

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 152 152 14
PDF Downloads 30 30 1