AN IMPROVED IMAGING AGENT FOR MALIGNANT-MELANOMA, BASED ON [NLE(4), D-PHE(7)]ALPHA-MELANOCYTE STIMULATING HORMONE

被引：12

作者：

BARD, DR

机构：

[1] Strangeways Research Laboratory, Worts' Causeway, Cambridge

来源：

NUCLEAR MEDICINE COMMUNICATIONS | 1995年 / 16卷 / 10期

关键词：

D O I：

10.1097/00006231-199510000-00010

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Two compounds have been synthesized based on [Nle(4),D-Phe(7)]alpha-melanocyte stimulating hormone (NDP-MSH) in which either one or two peptide sequences were covalently linked through their N'-termini to a single molecule of diethylenetriamine pentaacetic acid (DTPA). These two compounds (monoNDP-MSH-DTPA and bisNDP-MSH-DTPA, respectively) bound indium-111 (In-111) stably and showed hormonal activity as great or greater than cr-melanocyte stimulating hormone (alpha-MSH). Both compounds were able to target In-111 to Cloudman S91 melanomas in DBA2 mice. MonoNDP-MSH-DTPA gave the highest tumour:blood and tumour:tissue ratios and showed least unspecific radioactivity in the liver and kidney. Radioscintigraphy of mice showed good tumour localization of In-111 with both compounds, clear images being obtainable within 2 h of injection. Scans with monoNDP-MSH-DTPA showed some kidney and thyroid but no liver radioactivity, whereas bisNDP-MSH-DTPA gave extensive abdominal radioactivity, most of which was associated with the liver and kidneys. MonoNDP-MSH-DTPA was cleared from the tumour much less rapidly and gave more favourable tumour:blood ratios than other alpha-MSH derivatives previously investigated. It is concluded that monoNDP-MSH-DTPA offers promise as a melanoma imaging agent in man.

引用

页码：860 / 866

页数：7

共 18 条

[1]

Bard D.R., Malignant melanoma: Targeting strategies based on α-melanocyte stimulating hormone, Inflammopharmacology, 3, pp. 7-23, (1995)

[2]

Bard D.R., Knight C.G., Page-Thomas D.P., A chelating derivative of α-melanocyte stimulating hormone as a potential imaging agent for malignant melanoma, Br J Cancer, 62, pp. 919-922, (1990)

[3]

Bard D.R., Knight C.G., Page-Thomas D.P., Et al., The use of derivatives of α-MSH for targeting to melanomas in vivo, Targeting of Drugs 3: The Challenge of Peptides and Proteins, pp. 1-8, (1992)

[4]

Wraight E.P., Bard D.R., Maughan T.S., Et al., The use of a chelating derivative of alpha melanocyte stimulating hormone for the clinical imaging of malignant melanoma, Br J Radiol, 65, pp. 112-118, (1992)

[5]

Bard D.R., Wraight E.P., Knight C.G., BisMSH-DTPA: A potential imaging agent for malignant melanoma, Ann NY Acad Sci, 680, pp. 451-453, (1993)

[6]

Hadley M.E., Marwan M.M., Al-Obeidi F., Et al., Linear and cyclic alpha-melanotropin [4-10]-fragment analogues that exhibit superpotency and residual activity, Pigment Cell Res, 2, pp. 478-484, (1989)

[7]

Marks N., Stem F., Kastin A.J., Biodegradation of α-MSH and derived peptides by rat brain extracts and rat and human serum, Brain Res Bull, 1, pp. 591-593, (1976)

[8]

Bard D.R., Knight C.G., Page-Thomas D.P., Targeting of a chelating derivative of a short-chain analogue of α- melanocyte stimulating hormone to Cloudman S91 melanomas, Biochem Soc Trans, 18, pp. 882-883, (1990)

[9]

Bard D.R., Knight C.G., Wraight E.P., Et al., The use of MSH derivatives for targeting to melanomas, Targeting of Drugs 4: Advances in System Constructs, pp. 53-59, (1994)

[10]

Bard D.R., Potential imaging agents for melanoma based on an active analogue of a-melanocyte stimulating hormone, Drug Delivery, 2, pp. 73-80, (1995)

← 1 2 →