Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting

M. Chinol, G. Paganelli, F. Sudati, C. Meares, F. Fazio

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Tumour pretargeting techniques based on a three-step approach with the avidin/biotin system and associated with the high-energy beta-emitter yttrium-90 (90Y) have been applied with encouraging results in cancer therapy. While in-vivo stable binding of 90Y through a chelating agent like DOTA is essential for directly labelled monoclonal antibodies in the labelling of a fast clearing molecule like biotin, this may not be so important, since the time for catabolic processes to occur is drastically reduced. In this study, the biodistribution of 90Y bound to biotin through DTPA or DOTA was evaluated. Tumour-bearing mice received biotinylated antibody on day 1, avidin on day 2 and 90Y-labelled biotin on day 3. The biodistribution was determined 4 and 24 h after the injection of radiolabelled biotin. The majority of the injected dose was recovered in the urine 4 h after injection of both radiolabelled compounds. Higher bone uptake of 90Y was observed in animals administered 90Y-DTPA-biotin. In general, all organs including tumour showed higher accumulation of activity following the injection of 90Y-DTPA-biotin. Despite the lower levels of accumulation in the tumour after injection of 90Y-DOTA-biotin, the tumour-to-liver and tumour-to-bone ratios for the DOTA ligand were higher compared to DTPA. The higher tumour uptake observed after injection of 90Y-DTPA-biotin may be attributed to the presence of two biotin molecules in its dimeric structure. Our results indicate that the ideal 90Y-labelled biotin derivative for therapy studies should be formed from a DOTA core with two non-cleavable spacers, each ending with a biotin molecule.

Original languageEnglish (US)
Pages (from-to)176-182
Number of pages7
JournalNuclear Medicine Communications
Volume18
Issue number2
StatePublished - 1997

Fingerprint

Biotin
Pentetic Acid
Neoplasms
Injections
Avidin
Yttrium
Bone and Bones
Chelating Agents
Monoclonal Antibodies
Urine
Ligands
Antibodies

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Chinol, M., Paganelli, G., Sudati, F., Meares, C., & Fazio, F. (1997). Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting. Nuclear Medicine Communications, 18(2), 176-182.

Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting. / Chinol, M.; Paganelli, G.; Sudati, F.; Meares, C.; Fazio, F.

In: Nuclear Medicine Communications, Vol. 18, No. 2, 1997, p. 176-182.

Research output: Contribution to journalArticle

Chinol, M, Paganelli, G, Sudati, F, Meares, C & Fazio, F 1997, 'Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting', Nuclear Medicine Communications, vol. 18, no. 2, pp. 176-182.
Chinol, M. ; Paganelli, G. ; Sudati, F. ; Meares, C. ; Fazio, F. / Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting. In: Nuclear Medicine Communications. 1997 ; Vol. 18, No. 2. pp. 176-182.
@article{31a887e926814a598b78adb86013b668,
title = "Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting",
abstract = "Tumour pretargeting techniques based on a three-step approach with the avidin/biotin system and associated with the high-energy beta-emitter yttrium-90 (90Y) have been applied with encouraging results in cancer therapy. While in-vivo stable binding of 90Y through a chelating agent like DOTA is essential for directly labelled monoclonal antibodies in the labelling of a fast clearing molecule like biotin, this may not be so important, since the time for catabolic processes to occur is drastically reduced. In this study, the biodistribution of 90Y bound to biotin through DTPA or DOTA was evaluated. Tumour-bearing mice received biotinylated antibody on day 1, avidin on day 2 and 90Y-labelled biotin on day 3. The biodistribution was determined 4 and 24 h after the injection of radiolabelled biotin. The majority of the injected dose was recovered in the urine 4 h after injection of both radiolabelled compounds. Higher bone uptake of 90Y was observed in animals administered 90Y-DTPA-biotin. In general, all organs including tumour showed higher accumulation of activity following the injection of 90Y-DTPA-biotin. Despite the lower levels of accumulation in the tumour after injection of 90Y-DOTA-biotin, the tumour-to-liver and tumour-to-bone ratios for the DOTA ligand were higher compared to DTPA. The higher tumour uptake observed after injection of 90Y-DTPA-biotin may be attributed to the presence of two biotin molecules in its dimeric structure. Our results indicate that the ideal 90Y-labelled biotin derivative for therapy studies should be formed from a DOTA core with two non-cleavable spacers, each ending with a biotin molecule.",
author = "M. Chinol and G. Paganelli and F. Sudati and C. Meares and F. Fazio",
year = "1997",
language = "English (US)",
volume = "18",
pages = "176--182",
journal = "Nuclear Medicine Communications",
issn = "0143-3636",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Biodistribution in tumour-bearing mice of two 90Y-labelled biotins using three-step tumour targeting

AU - Chinol, M.

AU - Paganelli, G.

AU - Sudati, F.

AU - Meares, C.

AU - Fazio, F.

PY - 1997

Y1 - 1997

N2 - Tumour pretargeting techniques based on a three-step approach with the avidin/biotin system and associated with the high-energy beta-emitter yttrium-90 (90Y) have been applied with encouraging results in cancer therapy. While in-vivo stable binding of 90Y through a chelating agent like DOTA is essential for directly labelled monoclonal antibodies in the labelling of a fast clearing molecule like biotin, this may not be so important, since the time for catabolic processes to occur is drastically reduced. In this study, the biodistribution of 90Y bound to biotin through DTPA or DOTA was evaluated. Tumour-bearing mice received biotinylated antibody on day 1, avidin on day 2 and 90Y-labelled biotin on day 3. The biodistribution was determined 4 and 24 h after the injection of radiolabelled biotin. The majority of the injected dose was recovered in the urine 4 h after injection of both radiolabelled compounds. Higher bone uptake of 90Y was observed in animals administered 90Y-DTPA-biotin. In general, all organs including tumour showed higher accumulation of activity following the injection of 90Y-DTPA-biotin. Despite the lower levels of accumulation in the tumour after injection of 90Y-DOTA-biotin, the tumour-to-liver and tumour-to-bone ratios for the DOTA ligand were higher compared to DTPA. The higher tumour uptake observed after injection of 90Y-DTPA-biotin may be attributed to the presence of two biotin molecules in its dimeric structure. Our results indicate that the ideal 90Y-labelled biotin derivative for therapy studies should be formed from a DOTA core with two non-cleavable spacers, each ending with a biotin molecule.

AB - Tumour pretargeting techniques based on a three-step approach with the avidin/biotin system and associated with the high-energy beta-emitter yttrium-90 (90Y) have been applied with encouraging results in cancer therapy. While in-vivo stable binding of 90Y through a chelating agent like DOTA is essential for directly labelled monoclonal antibodies in the labelling of a fast clearing molecule like biotin, this may not be so important, since the time for catabolic processes to occur is drastically reduced. In this study, the biodistribution of 90Y bound to biotin through DTPA or DOTA was evaluated. Tumour-bearing mice received biotinylated antibody on day 1, avidin on day 2 and 90Y-labelled biotin on day 3. The biodistribution was determined 4 and 24 h after the injection of radiolabelled biotin. The majority of the injected dose was recovered in the urine 4 h after injection of both radiolabelled compounds. Higher bone uptake of 90Y was observed in animals administered 90Y-DTPA-biotin. In general, all organs including tumour showed higher accumulation of activity following the injection of 90Y-DTPA-biotin. Despite the lower levels of accumulation in the tumour after injection of 90Y-DOTA-biotin, the tumour-to-liver and tumour-to-bone ratios for the DOTA ligand were higher compared to DTPA. The higher tumour uptake observed after injection of 90Y-DTPA-biotin may be attributed to the presence of two biotin molecules in its dimeric structure. Our results indicate that the ideal 90Y-labelled biotin derivative for therapy studies should be formed from a DOTA core with two non-cleavable spacers, each ending with a biotin molecule.

UR - http://www.scopus.com/inward/record.url?scp=0030954927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030954927&partnerID=8YFLogxK

M3 - Article

C2 - 9076775

AN - SCOPUS:0030954927

VL - 18

SP - 176

EP - 182

JO - Nuclear Medicine Communications

JF - Nuclear Medicine Communications

SN - 0143-3636

IS - 2

ER -