Radiolabeled iodohypericin as tumor necrosis avid tracer: diagnostic and therapeutic potential

Abstract

It is estimated that 30–80% of solid tumor mass represents necrotic tissue that consists out of a significant number of dead and dying cells. The fact that these necrotic zones are restricted to dysplastic and malignant tissue and are rarely present in normal tissue makes necrosis an interesting target both for cancer diagnosis and therapy. In this study, the avidity of hypericin, [123I]iodohypericin and [131I]iodohypericin to tumor necrosis was explored for both diagnosis and therapy of experimental malignancies. The intratumoral distribution in RIF‐1 tumors was investigated by means of fluorescence microscopy (hypericin) and autoradiography ([123I]iodohypericin). Results show high uptake of the tracers in necrosis at 24 hr, lasting for up to 72 hr p.i. Ratios of activity of [123I]iodohypericin in necrotic tissue over viable tumor reached up to 19.63 ± 4.66, correlating with 9.20% ID/g in necrosis. Nude mice bearing RIF‐1 tumors that received three injections of 300 μCi over a 3‐week treatment period showed stabilization in tumor growth for 5 days, as measured by caliper and micro‐positron emission tomography using [18F]fluorodeoxyglucose. Based on these results, we suggest the potentials of radiolabeled hypericin (1) in diagnostic aspects including prognosis or staging assessment of bulky necrotic cancers, monitoring of treatments and therapeutic follow‐up; and (2) in cancer treatment based on tumor necrosis. In conclusion, we showed that hypericin radiolabeled with iodine is a necrosis avid tracer that can be used both as a tumor diagnostic and therapeutic.

Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging

“…It was recently discovered that hypericin has a peculiar affinity for necrotic tissues 10-18, independent of its photosensitivity. Several radiolabeled derivatives of hypericin, such as [ 123 I]iodohypericin 19-24 and [ 131 I]iodohypericin 25, have shown similar necrotic affinity in a number of pathological processes, including in animal models with organ infarctions or tumor necrosis. Thus, hypericin has also been recognized as a necrosis-avid contrast agent (NACA) 10, 18, 19, and is a focus of interest in relation to necrosis imaging.…”

“…Thus, hypericin has also been recognized as a necrosis-avid contrast agent (NACA) 10, 18, 19, and is a focus of interest in relation to necrosis imaging. Due to their high sensitivity and specificity toward necrotic tissues, NACAs have been used as specific magnetic resonance imaging (MRI) markers for noninvasive targeting of tissue necrosis in numerous disorders 19-24, 26-32. Application of NACAs include acute myocardial infarction identification 16, 28, 33, tissue viability evaluation 27, 30-32, assessment of therapeutic responses to drug treatment 14, and interventional procedures 26 in subjects with solid tumors.…”

Sodium cholate, a solubilizing agent for the necrosis avid radioiodinated hypericin in rabbits with acute myocardial infarction

“…The color code bar indicates the coding scheme for the radioactivity. Red color refers areas with the highest Van de Putte et al, 2012) and DMSO/PEG-400/water (25/60/ 15, v/v/v) (Cona et al, 2013a) have been reported. Pure DMSO as carrier of the poorly water soluble 123 I-Hyp/Hyp has also been used (Li et al, 2012).…”

Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy

“…As 131 I-Hyp alone has been documented to have little tumoricidal activity [18, 22], we deliberately did not include a control group of 131 I-Hyp treatment alone. Also, we minimized the radiation injury during all procedures.…”

“…Compared with some targeted drugs that just anchor to viable tumor tissues, hypericin could specifically and steadily bind to the tumor necrotic tissue with high target-to-nontarget ratios [16–19]. 131 I-Hyp has also been identified as a potential therapeutic radiopharmaceutical in the field of so-called necrosis target radiotherapy compared with other previously identified specific agents [18, 19]. …”