[¹²⁵I/¹²⁷I/¹³¹I]Iodorhodamine:  Synthesis, Cellular Localization, and Biodistribution in Athymic Mice Bearing Human Tumor Xenografts and Comparison with [^99mTc]Hexakis(2-methoxyisobutylisonitrile)

Abstract

The synthesis of halogenated rhodamine (Rh) derivatives was carried out by controlling the stoichiometry of the halogenating agents, bromine and iodine monochloride. In the no-carrier-added synthesis of radioiodinated rhodamine 123, direct labeling of rhodamine 123 (Rh 123) with Na125I/Na131I required the presence of the oxidant peracetic acid. 125I/131I-Rh 123 was synthesized in modest yields (40-45%). HPLC purification separated Rh 123 from its mono- and diiodo derivatives. Monohalogenation of Rh 123 did not alter the compound's ability to permeate viable cells and localize in mitochondria. 125I/131I-Rh 123 was stable in serum in vitro but rapidly metabolized after intravenous injection into mice. Consequently, scintigraphy and biodistribution data reveal poor targeting of subcutaneously growing human tumor xenografts. The results are compared to those obtained following the administration of [99mTc]hexakis(2-methoxyisobutylisonitrile) which also did not image human tumor xenografts in nude mice.

Synthesis of fluorine-18 labeled rhodamine B: A potential PET myocardial perfusion imaging agent

“…There is significant uptake in the gall bladder, and subsequently, the intestine. This observation is consistent with the results obtained by Harapanhalli, et al, who also observed excretion into the small intestine with minimal accumulation in the heart (Harapanhalli et al , 1998). We suspect that this may be due to hydrolysis of the ester in vivo .…”

“…Perhaps most significantly, Vora and Dhalla showed that non-radiolabeled rhodamine 123 accumulated in the rat heart (Vora et al , 1992). Additionally, Kassis and co-workers have investigated the potential use of radioiodinated rhodamine 123 in tumor diagnosis or therapy (Kinsey et al , 1987, Kinsey et al , 1989, Harapanhalli et al , 1998). …”

Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

“…The observed decomposition of the ester in mouse serum parallels the observations of Harapanhalli, et al who reported that approximately 10% of the iodinated rhodamine 123 was still present in mouse blood as the ester 2 h post-injection [29]. Vora and Dhalla also reported in vivo hydrolysis of non-labeled rhodamine 123 (a methyl ester) to rhodamine 110 (the acid form) in mice, but still noted high rhodamine uptake in the heart, perhaps because the larger physical quantity of the non-labeled material inhibited hydrolysis [24].…”

Nanoparticles as drug delivery agents specific for CNS: in vivo biodistribution

“…5 Rh-123 was selected as a marker for these biodistribution studies, because this fluorescent dye is able to cross the BBB in a negligible amount when administered intravenously (IV). [6][7][8] The ability of the NPs to act as a drug delivery agent for the CNS was assessed in previous studies dealing with several model drugs as loperamide, because this compound is unable to exert any antinociceptive effect when administered IV, being unable to cross the BBB. 9 Because a pharmacological assay (antinociceptive assay) allows the determination of the drug effect when it reaches the brain, loperamide has been used in many other studies dealing with drug delivery to the CNS.…”