Biodistribution study of <sup>99m</sup>Tc‐labeled LDL in B16‐melanoma‐bearing mice. Visualization of a preferential uptake by the tumor

Ponty, Emmanuelle; Carton, Michel; Soula, G; Favre, Gilles; Benaniba, Rachid; Boneu, A; Lucot, H

doi:10.1002/ijc.2910540311

Cited by 36 publications

(20 citation statements)

References 26 publications

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“…This is supported by the fact that B16 tumors are known to over-express LDL receptors. 13,26 The ratio of radioactivity above unity observed for all the organs after injection of 111 In-LDL is consistent with the presence of LDL receptors in non-cancerous cells. 24,27 The B16 melanoma showed up clearly on scintigraphy and exhibited marked radioactivity after injection of the 111 In-L-L tracer: B16 cells express the LDL receptor abundantly and the tumor is well vascularized.…”

Section: Discussionsupporting

confidence: 75%

Use of ¹¹¹In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Urizzi

Souchard

Ratovo

et al. 2003

Applied Organom Chemis

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The present study was designed to evaluate the potential of labeled low-density lipoprotein with 111 In using a lipid chelating agent (bis(stearylamide) of diethylenetriaminepentaacetic acid: L) to detect pancreatic tumors and melanoma in mice by gamma-scintigraphy. We compare the biodistribution of radioactivity and scintigraphic images in nude mice heterotransplanted with human cancerous pancreatic duct cells (Capan-1) and in mice transplanted with murine tumor cells (B16 melanoma). Biodistribution studies showed that radioactivity was twice as high in the Capan-1 xenograft after injection of the radiolabel than after injection of radiometal alone, and 34-fold higher in the B16 tumor. On gamma-scintigraphic imaging, the Capan-1 tumor was just visible, whereas the B16 melanoma was clearly imaged. The lack of contrast of the Capan-1 tumor compared with the B16 melanoma could be due to a poor vascularization.

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Section: Discussionsupporting

confidence: 75%

Use of ¹¹¹In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Urizzi

Souchard

Ratovo

et al. 2003

Applied Organom Chemis

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“…In previous studies, using [1251I]LDL, tumour-liver ratios of 1.5-2 were found (Lombardi et al, 1989;Ponty et al, 1993 (Angelin et al, 1983). The expression of LDL receptors on tumour cells, which lack remnant receptors, will be unaffected by the diet.…”

Section: Discussionmentioning

confidence: 90%

Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in vitro and in vivo in mice

Versluis¹,

Geel²,

Oppelaar³

et al. 1996

Br J Cancer

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Summary Selective delivery of cytotoxic anti-neoplastic drugs can diminish the severe side-effects associated with these drugs. Many malignant tumours express high levels of low-density lipoprotein (LDL) receptors on their membranes. Therefore, LDL may be used as a carrier to obtain selective delivery of anti-neoplastic drugs to tumours. The present study was performed to investigate the feasibility of the murine B16 tumour/mouse model for the evaluation of LDL-mediated tumour therapy. LDL binds with high affinity to LDL receptors on cultured B16 cells (Kd, 5.9+2.3 Yg ml -; Bmax, 206+23 ng LDL mg-1 cell protein). After binding and internalisation, LDL was very efficiently degraded: 724+ 19 ng LDL mg -cell protein h-'. Chloroquine and ammonium chloride completely inhibited the degradation of LDL by the B16 cells, indicating involvement of lysosomes. LDL receptors were down-regulated by 70% after preincubation of B16 cells with 300 jg ml-l LDL, indicating that their expression is regulated by intracellular cholesterol. To evaluate the uptake of LDL by the B16 tumour in vivo, tissue distribution studies were performed in C57/Bl mice inoculated with B16 tumours. For these experiments, LDL was radiolabelled with tyramine cellobiose, a non-degradable label, which is retained in cells after uptake. At 24 h after injection of LDL, the liver, adrenals and the spleen were found to be the major organs involved in LDL uptake, with tissue-serum (T/S) ratios of 0.82+0.08, 1.17 + 0.20 and 0.69 + 0.08 respectively. Of all the other tissues, the tumour showed the highest uptake of LDL (T/S ratio of 0.40+0.07). A large part of the LDL uptake was receptor mediated, as the uptake of methylated LDL was much lower. Although the LDL uptake by the liver, spleen and adrenals is higher than that by the tumour, the LDL receptor-mediated uptake by these organs may be selectively down-regulated by methods that do not affect the expression of LDL receptors on tumour cells. It is concluded that the B16 tumour-bearing mouse constitutes a good model to evaluate the effectiveness of LDL-mediated delivery of cytotoxic (pro)drugs to tumours in vivo.

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“…PONTY et al (1993) demonstraram acúmulo de LDL humana marcada com Tc em tumores implantados (melanoma, B16F10) de camundongos (C57bl/6). Após oito dias do implante do tumor, o acúmulo de LDL detectado era maior no tumor do que no fígado ou rim.…”

Section: Emulsões Lipídicasunclassified

Receptores De LDL : Alvo Para Drogas Anti-Neoplasicas

Fávero¹,

Bydlowski²

2008

Publ. Biologicas

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RESUMOO direcionamento e acúmulo de drogas em tumores é um dos grandes desafi os das quimioterapias. Os principais benefícios desta estratégia terapêutica seriam o aumento da potência farmacoterapêutica e a diminuição dos efeitos colaterais. Dentre as possibilidades envolvendo o direcionamento dos quimioterápicos, estão o uso de enzimas, anticorpos, lipossomas e microemulsões. O presente trabalho objetiva mostrar as possibilidades da utilização dos receptores da lipoproteína de baixa densidade (LDLr) como alvo para o direcionamento de quimioterápicos. Esta hipótese vem sendo estudada desde meados do século passado e é fruto da descoberta da importância dos LDLr em tumores com crescimento descontrolado. Esta é a principal via de fornecimento de colesterol para a produção de membranas para as células tumorais que apresentam uma maior expressão de LDLr.Palavras-chave: Câncer. LDL. Receptores LDL. Quimioterapia seletiva. ABSTRACTDrug targeting and accumulation in tumors are great challenges of chemotherapy. The main benefi ts of this therapeutical strategy would be the increase of the pharmacotherapeutical potency and the reduction of collateral effects. Amongst the possibilities involving chemotherapic targeting are the use of enzymes, antibodies, liposomes and microemulsions. The aim of the present study is to show the possibilities of the use of low density lipoprotein receptors (LDLr) as a target for chemotherapics. This hypothesis has been studied since the middle of the last century and it derives from the discovery of the importance of LDLr in tumors with uncontrolled growth. This is the main way used by tumor cells to supply the cholesterol needed in the production of membranes, because these cells present a more expressive amount of LDLr.

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Biodistribution study of ^99mTc‐labeled LDL in B16‐melanoma‐bearing mice. Visualization of a preferential uptake by the tumor

Cited by 36 publications

References 26 publications

Use of ¹¹¹In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Use of ¹¹¹In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in vitro and in vivo in mice

Receptores De LDL : Alvo Para Drogas Anti-Neoplasicas

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Biodistribution study of 99mTc‐labeled LDL in B16‐melanoma‐bearing mice. Visualization of a preferential uptake by the tumor

Cited by 36 publications

References 26 publications

Use of 111In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Use of 111In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in vitro and in vivo in mice

Receptores De LDL : Alvo Para Drogas Anti-Neoplasicas

Contact Info

Product

Resources

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Biodistribution study of ^99mTc‐labeled LDL in B16‐melanoma‐bearing mice. Visualization of a preferential uptake by the tumor

Use of ¹¹¹In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors

Use of ¹¹¹In–L–LDL radiotracers to detect human pancreatic and mice melanoma tumors