Preclinical evaluation of [111In-DTPA-Pro1,Tyr4]bombesin, a new radioligand for bombesin receptor scintigraphy

Breeman, W. A. P.; Jong, Marion de; Bernard, Bert F.; Kwekkeboom, Dik J.; Srinivasan, Ananth; Schaar, Michael; Xeerden, W. van; Visser, T.; Krenning, Eric P.

doi:10.1097/00006231-200006000-00091

Cited by 10 publications

(13 citation statements)

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“…Moreover, novel and specific Y 1 ligands have recently been reported [37] that need to be linked to chelators for radioimaging. While several radioligands specific for GRP receptors have been synthesized [38,39,40], only the 99m Tc-labelled bombesin analogue RP527 has been used to target human tumours up to now [34,35]. The present study may therefore trigger and motivate the initiation of new preclinical and clinical studies in these directions.…”

Section: Discussionmentioning

confidence: 96%

Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting

2002

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Breast cancers can express different types of peptide receptors such as somatostatin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP) and NPY(Y(1)) receptors. The aim of this in vitro study was to evaluate which is the most appropriate peptide receptor or peptide receptor combination for in vivo diagnostic and therapeutic targeting of breast cancers. Seventy-seven primary breast cancers and 15 breast cancer lymph node metastases were investigated in vitro for their expression of somatostatin, VPAC(1), GRP and NPY(Y(1)) receptors using in vitro receptor autoradiography on successive tissue sections with (125)I-[Tyr(3)]-octreotide, (125)I-VIP, (125)I-[Tyr(4)]-bombesin and (125)I-[Leu(31),Pro(34)]-PYY respectively. This study identified two groups of tumours: a group of 68 tumours (88%) with at least one receptor expressed at high density (>2,000 dpm/mg tissue) that may provide a strong predictive value for successful in vivo targeting, and a group of nine tumours (12%) with no receptors or only a low density of them (<2,000 dpm/mg tissue). In the group with high receptor density, 50 of the 68 tumours (74%) expressed GRP receptors, 45 (66%) expressed NPY(Y(1)) receptors, 25 (37%) expressed VPAC(1) receptors and 14 (21%) expressed somatostatin receptors. Mean density was 9,819+/-530 dpm/mg tissue for GRP receptors, 9,135+/-579 dpm/mg for NPY(Y(1)) receptors, 4,337+/-528 dpm/mg for somatostatin receptors and 3,437+/-306 dpm/mg for VPAC(1) receptors. It is of note that tumours expressing NPY(Y(1)) or GRP receptors, or both, were found in 63/68 (93%) cases. Lymph node metastases showed a similar receptor profile to the corresponding primary tumour. This in vitro study strongly suggests that the combination of radiolabelled GRP and Y(1) analogues should allow targeting of breast carcinomas and their lymph node metastases for in vivo peptide receptor scintigraphy and radiotherapy.

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Section: Discussionmentioning

confidence: 96%

Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting

2002

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“…Targeting these with labeled bombesin is a promising approach for in vivo targeting of GRP receptor-expressing cancers. 99m Tc or 111 In-labeled bombesin-chelator conjugates compounds maintain high binding affinities for GRP receptors [136][137][138]. Some of these radiopharmaceuticals have been studied in clinical trials [139,140].…”

Section: Peptide Receptorsmentioning

confidence: 99%

Nuclear imaging of molecular processes in cancer

2009

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Molecular imaging using radionuclides has brought about the possibility to image a wide range of molecular processes using radiotracers injected into the body at very low concentrations that should not perturb the processes being studied. Examples include specific peptide receptor expression, angiogenesis, multi drug resistance, hypoxia, glucose metabolism, and many others. This article presents an overview, aimed at the non-specialist in imaging, of the radionuclide imaging technologies positron emission tomography and single photon radionuclide imaging, and some of the molecules labeled with gamma- and positron-emitting radioisotopes that have been, or are being, developed for research and clinical applications in cancer.

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“…in the circulation, which can release the cytotoxic radical before the targeting is completed . Preclinical and clinical results with new radioligands, developed for BN-receptor scintigraphy, also indicate that BN analogues can accumulate in BN receptor-positive tumours, further supporting the theory that BN receptors can be used for targeted chemotherapy (Breeman et al, 1999;Van de Wiele et al, 2000).…”

Section: Discussionmentioning

confidence: 69%

Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215

et al. 2002

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Some brain tumours, such as glioblastomas express high levels of receptors for bombesin/gastrin releasing peptide. We investigated whether bombesin/gastrin releasing peptide receptors found in glioblastoma cell lines can be utilised for targeting of a cytotoxic bombesin analogue, AN-215 consisting of a potent derivative of doxorubicin, 2-pyrrolino-doxorubicin (AN-201) linked to a bombesin-like peptide carrier. This study reports the effect of AN-215 on the growth of U-87MG human glioblastomas xenografted into nude mice. High affinity binding of AN-215 to U-87MG tumours was characterised by an IC 50 value of 4.0+0.1 nM, as determined by radioreceptor assays. mRNA analyses revealed the presence of mRNA for BN receptor subtypes 1 and 2. Treatment with AN-215 significantly (P50.05) extended tumour doubling time from 4.54+0.2 days to 8.18+1.8 days and inhibited tumour growth as demonstrated by a 69.6% reduction in final tumour volume (P50.001) and a 64.6% decrease in tumour weight as compared to controls. Cytotoxic radical AN-201 at the same dose was ineffective. The antitumour effect of AN-215 could be blocked by pretreatment with an excess of a bombesin antagonist, indicating that the action of this cytotoxic analogue is receptor-mediated. Our results suggest that patients with inoperable brain tumours such as malignant gliomas may benefit from targeted chemotherapy based on cytotoxic bombesin analogue AN-215.

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Preclinical evaluation of [111In-DTPA-Pro1,Tyr4]bombesin, a new radioligand for bombesin receptor scintigraphy

Cited by 10 publications

References 0 publications

Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting

Co-expressed peptide receptors in breast cancer as a molecular basis for in vivo multireceptor tumour targeting

Nuclear imaging of molecular processes in cancer

Effective treatment of experimental U-87MG human glioblastoma in nude mice with a targeted cytotoxic bombesin analogue, AN-215

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