J Korean Med Sci.  2004 Oct;19(5):647-651. 10.3346/jkms.2004.19.5.647.

Intratumoral Injection of (188)Re labeled Cationic Polyethylenimine Conjugates: A Preliminary Report

• Kim EM
• Jeong HJ
• Heo YJ
• Moon HB
• Bom HS
• Kim CG

• KMID: 1733502
• DOI: http://doi.org/10.3346/jkms.2004.19.5.647

Abstract

(188)Re(Rhenium) is easily obtained from an in-house (188)W/(188)Re generator that is similar to the current (99)Mo/(99m)Tc generator, making it very convenient for clinical use. This characteristic makes this radionuclide a promising candidate as a therapeutic agent. Polyethylenimine (PEI) is a cationic polymer and has been used as a gene delivery vector. Positively charged materials interact with cellular blood components, vascular endothelium, and plasma proteins. In this study, the authors investigated whether intratumoral injection of (188)Re labeled transferrin (Tf)-PEI conjugates exert the effect of radionuclide therapy against the tumor cells. When the diameters of the Ramos lymphoma (human Burkitt's lymphoma) xenografted tumors reached approximately 1 cm, 3 kinds of (188)Re bound compounds (HYNIC-PEI-Tf, HYNIC-PEI, (188)Re perrhenate) were injected directly into the tumors. There were increases in the retention of (188)Re inside the tumor when PEI was incorporated with (188)Re compared to the use of free 188Re. The (188)Re HYNIC-Tf-PEI showed the most retention inside the tumor (retention rate=approximately 97%). H&E stain of isolated tumor tissues showed that (188)Re labeled HYNIC-PEI-Tf caused extensive tumor necrosis. These results support (188)Re HYNIC-PEI-Tf as being a useful radiopharmaceutical agent to treat tumors when delievered by intratumoral injection.

Keyword

Rhenium; Polyethylenimine; Transferrin; Lymphoma

MeSH Terms

Animals
Burkitt Lymphoma/pathology/*radiotherapy
Cations
Female
Injections, Intralesional
Mice
Mice, Inbred BALB C
Pilot Projects
Polyethyleneimine/chemistry/*pharmacology
Radioisotopes/chemistry/*pharmacology
Research Support, Non-U.S. Gov't
Rhenium/chemistry/*pharmacology

Figure

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  Fig. 1 Gamma images of Ramos lymphoma xenografted nude mice 10 min, 2 hr, and 12 hr after intratumoral injection. (A) Of three kinds of 188Re conjugates, 188Re HYNIC-PEI-Tf showed the highest retention rate inside the tumor and relatively no leakage from the tumor when radionuclides were injected intratumorally. (B) With time, 188Re HYNIC-PEI escaped from the tumor with some extent (approximately 15%) and accumulated into the lung and liver. (A) 188Re HYNIC-PEI-Tf injected mouse, (B) 188Re HYNIC-PEI injected mouse, (C) 188Re perrhenate injected mouse. L, liver; T, tumor; ch, chest; th, thyroid; S, stomach; B, bladder.

• 

  Fig. 2 Hematoxylin-eosin staining obtained 48 hr after intratumoral injection. (A, B) Histological findings (H&E, original magnification ×10, ×200) demonstrate that wide central necrosis with peripheral viable cells is shown when 188Re HYNIC-PEI-Tf is injected, but (C, D, H&E ×10, ×200) no significant necrosis when 188Re perrhenate injected. T, tumor; N, necrosis; M, muscle.

• 

  Fig. 3 The result of RT-PCR for Tf-receptor in Ramos lymphoma cells. The result demonstrates that Ramos lymphoma cells had mRNA of human Tf-receptor. Lane 1: β-actin as control, Lane 2: Tf-R. MK: Molecular size marker.

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