Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP)

N. J. Parks, T. G. Kawakami, M. J. Avila, R. White, G. R. Cain, S. D. Raaka, W. Hornoff, P. Fisher, Peter F Moore, J Anthony Seibert, J. Garlich, J. Simon, R. Champlin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

β-emitting 166Ho (t1/2 = 26.78 hours, E(β)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/ kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The β particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

Original languageEnglish (US)
Pages (from-to)318-325
Number of pages8
JournalBlood
Volume82
Issue number1
StatePublished - Jul 1 1993

Fingerprint

Ablation
Bone Marrow Transplantation
Radio
Bone
Bone Marrow
Dogs
Bone and Bones
Radiopharmaceuticals
Transplants
Biopsy
Radioactivity
Chelating Agents
Dosimetry
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid)
phosphonic acid
Whole-Body Irradiation
Hematopoiesis
Metals
Cells
Skeleton

ASJC Scopus subject areas

  • Hematology

Cite this

Parks, N. J., Kawakami, T. G., Avila, M. J., White, R., Cain, G. R., Raaka, S. D., ... Champlin, R. (1993). Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP). Blood, 82(1), 318-325.

Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP). / Parks, N. J.; Kawakami, T. G.; Avila, M. J.; White, R.; Cain, G. R.; Raaka, S. D.; Hornoff, W.; Fisher, P.; Moore, Peter F; Seibert, J Anthony; Garlich, J.; Simon, J.; Champlin, R.

In: Blood, Vol. 82, No. 1, 01.07.1993, p. 318-325.

Research output: Contribution to journalArticle

Parks, NJ, Kawakami, TG, Avila, MJ, White, R, Cain, GR, Raaka, SD, Hornoff, W, Fisher, P, Moore, PF, Seibert, JA, Garlich, J, Simon, J & Champlin, R 1993, 'Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP)', Blood, vol. 82, no. 1, pp. 318-325.
Parks NJ, Kawakami TG, Avila MJ, White R, Cain GR, Raaka SD et al. Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP). Blood. 1993 Jul 1;82(1):318-325.
Parks, N. J. ; Kawakami, T. G. ; Avila, M. J. ; White, R. ; Cain, G. R. ; Raaka, S. D. ; Hornoff, W. ; Fisher, P. ; Moore, Peter F ; Seibert, J Anthony ; Garlich, J. ; Simon, J. ; Champlin, R. / Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP). In: Blood. 1993 ; Vol. 82, No. 1. pp. 318-325.
@article{f5162086b9204081ac254e5f0f245bed,
title = "Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP)",
abstract = "β-emitting 166Ho (t1/2 = 26.78 hours, E(β)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/ kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The β particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.",
author = "Parks, {N. J.} and Kawakami, {T. G.} and Avila, {M. J.} and R. White and Cain, {G. R.} and Raaka, {S. D.} and W. Hornoff and P. Fisher and Moore, {Peter F} and Seibert, {J Anthony} and J. Garlich and J. Simon and R. Champlin",
year = "1993",
month = "7",
day = "1",
language = "English (US)",
volume = "82",
pages = "318--325",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "1",

}

TY - JOUR

T1 - Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP)

AU - Parks, N. J.

AU - Kawakami, T. G.

AU - Avila, M. J.

AU - White, R.

AU - Cain, G. R.

AU - Raaka, S. D.

AU - Hornoff, W.

AU - Fisher, P.

AU - Moore, Peter F

AU - Seibert, J Anthony

AU - Garlich, J.

AU - Simon, J.

AU - Champlin, R.

PY - 1993/7/1

Y1 - 1993/7/1

N2 - β-emitting 166Ho (t1/2 = 26.78 hours, E(β)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/ kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The β particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

AB - β-emitting 166Ho (t1/2 = 26.78 hours, E(β)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/ kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The β particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

UR - http://www.scopus.com/inward/record.url?scp=0027175824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027175824&partnerID=8YFLogxK

M3 - Article

VL - 82

SP - 318

EP - 325

JO - Blood

JF - Blood

SN - 0006-4971

IS - 1

ER -