Transbilayer phospholipids molecular imaging

Belhocine, Tarik; Prato, Frank S.

doi:10.1186/2191-219x-1-17

Cited by 14 publications

(14 citation statements)

References 77 publications

(84 reference statements)

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“…In nude mice bearing subcutaneous RIF-1, stabilization in tumor growth for 5 days was reported after three injections of only 131 I-Hyp over a 3-week treatment period 79. In a rat model of liver R1, tumor size at 8 days after treatment was significantly smaller in a SMSDTTS treated group compared with the vehicle-control group as well as the single-targeting groups that were treated with CA4P or 131 I-Hyp solely (p<0.01) within 8 days 11,98. More recently, prolonged survival was found (p<0.01) in a murine model of subcutaneous RIF-1 in SMSDTTS treated group compared with the vehicle control and single CA4P groups, with a median survival 33, 22, and 21 days, and, at day 15, the corresponding tumor doubling times of 7.8 ± 2.8, 4.5 ± 0.5, and 4.4 ± 0.67 days, respectively 82.…”

Section: Tumoricidal Effectsmentioning

confidence: 98%

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

Li¹,

Oyen²,

Verbruggen³

et al. 2013

J. Cancer

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Hitting the evasive tumor cells proves challenging in targeted cancer therapies. A general and unconventional anticancer approach namely small molecule sequential dual-targeting theragnostic strategy (SMSDTTS) has recently been introduced with the aims to target and debulk the tumor mass, wipe out the residual tumor cells, and meanwhile enable cancer detectability. This dual targeting approach works in two steps for systemic delivery of two naturally derived drugs. First, an anti-tubulin vascular disrupting agent, e.g., combretastatin A4 phosphate (CA4P), is injected to selectively cut off tumor blood supply and to cause massive necrosis, which nevertheless always leaves peripheral tumor residues. Secondly, a necrosis-avid radiopharmaceutical, namely 131I-hypericin (131I-Hyp), is administered the next day, which accumulates in intratumoral necrosis and irradiates the residual cancer cells with beta particles. Theoretically, this complementary targeted approach may biologically and radioactively ablate solid tumors and reduce the risk of local recurrence, remote metastases, and thus cancer mortality. Meanwhile, the emitted gamma rays facilitate radio-scintigraphy to detect tumors and follow up the therapy, hence a simultaneous theragnostic approach. SMSDTTS has now shown promise from multicenter animal experiments and may demonstrate unique anticancer efficacy in upcoming preliminary clinical trials. In this short review article, information about the two involved agents, the rationale of SMSDTTS, its preclinical antitumor efficacy, multifocal targetability, simultaneous theragnostic property, and toxicities of the dose regimens are summarized. Meanwhile, possible drawbacks, practical challenges and future improvement with SMSDTTS are discussed, which hopefully may help to push forward this strategy from preclinical experiments towards possible clinical applications.

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Section: Tumoricidal Effectsmentioning

confidence: 98%

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

Li¹,

Oyen²,

Verbruggen³

et al. 2013

J. Cancer

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“…Increased phospholipid production [48], activated microglia [49], and astrogliosis [50] are neuroinflammatory processes that are amenable to quantification using PET. However, to date, only microglial activation has been reported in Tg models expressing amyloid or tau pathology phenotypes.…”

Section: Feature Reviewmentioning

confidence: 99%

MicroPET imaging and transgenic models: a blueprint for Alzheimer's disease clinical research

Zimmer

Parent

Cuello

et al. 2014

Trends in Neurosciences

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“…The above-described reports of hypericin selectively binding to cholesterol or the phospholipid targets PS and PE remain to be verified 67]. As hypericin has various subcellular distributions—including plasma membrane, endoplasmic reticulum (ER), mitochondria, lysosome, and Golgi apparatus 68, 69]—the observed selectivity of hypericin for cholesterol 65 or PS and PE 66, 67 might only occur because these molecules are the first to be encountered as hypericin enters cells.…”

Section: The Mechanism Of Necrosis Avidity Behind Hypericinmentioning

confidence: 99%

“…As hypericin has various subcellular distributions—including plasma membrane, endoplasmic reticulum (ER), mitochondria, lysosome, and Golgi apparatus 68, 69]—the observed selectivity of hypericin for cholesterol 65 or PS and PE 66, 67 might only occur because these molecules are the first to be encountered as hypericin enters cells. It is also possible that, due to the high permeability of capillaries in tumor tissue and tumor cell membranes, PS and PE in the internal leaflet of the tumor cell membrane may be exposed to some extent, like necrotic cells.…”

Section: The Mechanism Of Necrosis Avidity Behind Hypericinmentioning

confidence: 99%

“…Its radiolabeled derivative, 99m Tc-HYNIC-duramycin, has been successfully applied in myocardial infarction imaging in a rat model of ischemia-reperfusion 74. Duramycin reportedly targets PE, which is a main lipid component in the phospholipid bilayer structure and is exposed to duramycin after cell death 67. Radiolabeled antimyosin MAb ( 99m Tc-antimyosin or 111 In-antimyosin) reportedly has selective affinity for the heavy chain of intracellular myosin, because it is exposed after necrotic cell death.…”

Section: The Mechanism Of Necrosis Avidity Behind Hypericinmentioning

confidence: 99%

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

Jiang¹,

Jichen²,

Ni³

et al. 2013

Theranostics

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Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [123I]iodohypericin, [124I]iodohypericin, and [131I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin.

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Transbilayer phospholipids molecular imaging

Cited by 14 publications

References 77 publications

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

Small Molecule Sequential Dual-Targeting Theragnostic Strategy (SMSDTTS): from Preclinical Experiments towards Possible Clinical Anticancer Applications

MicroPET imaging and transgenic models: a blueprint for Alzheimer's disease clinical research

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

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