A 4-methyl-substituted Meta-iodobenzylguanidine Analogue with Prolonged Retention in Human Neuroblastoma Cells

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2004 Jun 19

PMID 15205923

Citations 3

Authors

Ganesan Vaidyanathan

Philip C Welsh

Katia C Vitorello

Stacey Snyder

Henry S Friedman

Michael R Zalutsky

Affiliations

Soon will be listed here.

Abstract

Purpose: As a part of our efforts to develop a meta-iodobenzylguanidine (MIBG) analogue with improved characteristics for the diagnosis and treatment of neuroendocrine tumours, 3-[131I]iodo-4-methyl-benzylguanidine ([131I]MeIBG) has been developed. The purpose of this study was to evaluate [131I]MeIBG in vitro using the uptake-1 positive SK-N-SH neuroblastoma cell line and in vivo in normal mice and mice bearing human neuroblastoma xenografts.

Methods: The ability of SK-N-SH human neuroblastoma cells to retain [131I]MeIBG in vitro over a period of 4 days, in comparison to [125I]MIBG, was determined by a paired-label assay. Paired-label biodistributions of [131I]MeIBG and [125I]MIBG were performed in normal mice as well as in athymic mice bearing SK-N-SH and IMR-32 human neuroblastoma xenografts.

Results: Retention of [131I]MeIBG by SK-N-SH cells in vitro was increased by factors of 1.2, 1.5, 2.0, 2.5 and 3.1 compared with [125I]MIBG at 8, 24, 48, 72 and 96 h, respectively. In normal mice, the uptake of [131I]MeIBG in the heart was similar to that of [125I]MIBG at 1 and 4 h; in contrast, myocardial uptake of [131I]MeIBG was 1.6-fold higher than that of [125I]MIBG (p<0.05) at 24 h. When mice were pre-treated with the uptake-1 inhibitor desipramine (DMI), the heart uptake of both tracers was reduced to about half that in untreated controls at 1 h post injection (p<0.05). The hepatic uptake of [131I]MeIBG was two- to threefold lower than that of [125I]MIBG. On the other hand, blood levels of [131I]MeIBG were substantially higher (up to sixfold), especially at early time points. Uptake of [131I]MeIBG in heart and tumour at 1 h in the murine SK-N-SH model was specific and comparable to that of [125I]MIBG. However, [131I]MeIBG uptake was 1.6- to 1.7-fold lower than that of [125I]MIBG over 4-48 h. While the uptake of both tracers in IMR32 xenografts was similar, it was not uptake-1 mediated.

Conclusion: Introduction of a methyl group at the 4-position of MIBG seems to be advantageous in terms of higher tumour retention in vitro and lower hepatic uptake in vivo. However, the slower blood clearance of MeIBG may be problematic for some applications.

Citing Articles

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References

Vaidyanathan G, Friedman H, Keir S, Zalutsky M . Localisation of [131I]MIBG in nude mice bearing SK-N-SH human neuroblastoma xenografts: effect of specific activity. Br J Cancer. 1996; 73(10):1171-7. PMC: 2074506. DOI: 10.1038/bjc.1996.226. View

Cano G, Sved A, Rinaman L, Rabin B, Card J . Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing. J Comp Neurol. 2001; 439(1):1-18. DOI: 10.1002/cne.1331. View

Jaques Jr S, Tobes M, Sisson J, Baker J, Wieland D . Comparison of the sodium dependency of uptake of meta-lodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol. 1984; 26(3):539-46. View

Kelley S, GROTA L, Felten S, Madden K, Felten D . Norepinephrine in mouse spleen shows minor strain differences and no diurnal variation. Pharmacol Biochem Behav. 1996; 53(1):141-6. DOI: 10.1016/0091-3057(95)02006-3. View

Sisson J, Shulkin B . Nuclear medicine imaging of pheochromocytoma and neuroblastoma. Q J Nucl Med. 1999; 43(3):217-23. View

Armour A, Mairs R, Gaze M, Wheldon T . Modification of meta-iodobenzylguanidine uptake in neuroblastoma cells by elevated temperature. Br J Cancer. 1994; 70(3):445-8. PMC: 2033365. DOI: 10.1038/bjc.1994.325. View

Patel A, Iskandrian A . MIBG imaging. J Nucl Cardiol. 2002; 9(1):75-94. DOI: 10.1067/mnc.2002.121471. View

Montaldo P, Raffaghello L, Guarnaccia F, Pistoia V, Garaventa A, Ponzoni M . Increase of metaiodobenzylguanidine uptake and intracellular half-life during differentiation of human neuroblastoma cells. Int J Cancer. 1996; 67(1):95-100. DOI: 10.1002/(SICI)1097-0215(19960703)67:1<95::AID-IJC16>3.0.CO;2-B. View

Tang H, da Silva A, Matthay K, Price D, Huberty J, Hawkins R . Neuroblastoma imaging using a combined CT scanner-scintillation camera and 131I-MIBG. J Nucl Med. 2001; 42(2):237-47. View

10.

Tepmongkol S, Heyman S . 131I MIBG therapy in neuroblastoma: mechanisms, rationale, and current status. Med Pediatr Oncol. 1999; 32(6):427-31; discussion 432. DOI: 10.1002/(sici)1096-911x(199906)32:6<427::aid-mpo6>3.0.co;2-t. View

11.

Vaidyanathan G, Zalutsky M . No-carrier-added synthesis of meta-[131I]iodobenzylguanidine. Appl Radiat Isot. 1993; 44(3):621-8. DOI: 10.1016/0969-8043(93)90179-e. View

12.

Biedler J, Helson L, Spengler B . Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973; 33(11):2643-52. View

13.

Hattori N, Schwaiger M . Metaiodobenzylguanidine scintigraphy of the heart: what have we learnt clinically?. Eur J Nucl Med. 2000; 27(1):1-6. DOI: 10.1007/s002590050505. View

14.

Vaidyanathan G, Zhao X, Strickland D, Zalutsky M . No-carrier-added iodine-131-FIBG: evaluation of an MIBG analog. J Nucl Med. 1997; 38(2):330-4. View

15.

Vaidyanathan G, Shankar S, Affleck D, Alston K, Norman J, Welsh P . Meta-iodobenzylguanidine derivatives containing a second guanidine moiety. Bioorg Med Chem. 2004; 12(7):1649-56. DOI: 10.1016/j.bmc.2004.01.026. View

16.

Lee H, Inbasekaran M, Wieland D, Sherman P, Fisher S, Mangner T . Development of a kit-form analog of metaiodobenzylguanidine. J Nucl Med. 1986; 27(2):256-67. View

17.

Khanna C, Jaboin J, Drakos E, Tsokos M, Thiele C . Biologically relevant orthotopic neuroblastoma xenograft models: primary adrenal tumor growth and spontaneous distant metastasis. In Vivo. 2002; 16(2):77-85. View

18.

Vaidyanathan G, Affleck D, Zalutsky M . Validation of 4-[fluorine-18]fluoro-3-iodobenzylguanidine as a positron-emitting analog of MIBG. J Nucl Med. 1995; 36(4):644-50. View

19.

Yanik G, Levine J, Matthay K, Sisson J, Shulkin B, Shapiro B . Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma. J Clin Oncol. 2002; 20(8):2142-9. DOI: 10.1200/JCO.2002.08.124. View

20.

Rutgers M, Gubbels A, Hoefnagel C, VOUTE P, Smets L . A human neuroblastoma xenograft model for [131I]-metaiodobenzylguanidine (MIBG) biodistribution and targeted radiotherapy. Prog Clin Biol Res. 1991; 366:471-8. View