Estimated Human Absorbed Dose of 111In-BPAMD as a New Bone-Seeking SPECT-Imaging Agent
An early diagnosis of bone metastasis is very
important for making a right decision on a subsequent therapy. One
of the most important steps to be taken initially, for developing a new
radiopharmaceutical is the measurement of organ radiation exposure
dose. In this study, the dosimetric studies of a novel agent for
SPECT-imaging of the bone metastasis, 111In-(4-
{[(bis(phosphonomethyl))carbamoyl]methyl}7,10bis(carboxymethyl)
-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (111In-BPAMD)
complex, have been carried out to estimate the dose in human organs
based on the data derived from mice. The radiolabeled complex was
prepared with high radiochemical purity in the optimal conditions.
Biodistribution studies of the complex was investigated in the male
Syrian mice at the selected times after injection (2, 4, 24 and 48 h).
The human absorbed dose estimation of the complex was made based
on data derived from the mice by the radiation absorbed dose
assessment resource (RADAR) method. 111In-BPAMD complex was prepared with high radiochemical
purity >95% (ITLC) and specific activities of 2.85 TBq/mmol. Total
body effective absorbed dose for 111In-BPAMD was 0.205
mSv/MBq. This value is comparable to the other 111In clinically used
complexes. The results show that the dose with respect to the critical
organs is satisfactory within the acceptable range for diagnostic
nuclear medicine procedures. Generally, 111In-BPAMD has
interesting characteristics and it can be considered as a viable agent
for SPECT-imaging of the bone metastasis in the near future.
[1] IAEA-TECDOC-1549, “Criteria for Palliation of Bone Metastases-
Clinical Applications,”. Austria, Vienna: IAEA; 2007.
[2] A. Lipton, “Pathophysiology of Bone Metastases: How This Knowledge
May Lead to Therapeutic Intervention,” J. Support. Oncol. vol. 2, pp.
205-20, 2004.
[3] M. Fellner, B. Biesalski, N. Bausbacher, V. Kubícek, P. Hermann, F.
Rösch, O. Thews, “68Ga-BPAMD: PET-imaging of bone metastases with
a generator based positron emitter,” Nucl. Med. Biol. vol. 39, pp. 993–9,
2012.
[4] G. Zettinig, T. Leitha, B. Niederle, K. Kaserer, A. Becherer, K. Kletter.
et al. “FDG positron emission tomographic, radioiodine, and MIBI
imaging in a patient with poorly differentiated insular thyroid
carcinoma,” Clin. Nucl. Med. Vol. 26, pp. 599–601, 2001.
[5] H. Yousefnia, A.R. Jalilian, S. Zolghadri, A. Mirzaei, A. Bahrami-
Samani, M. Mirzaii, M. Ghannadi, “Development of 111In DOTMP for
dosimetry of bone pain palliation agents,” J. Radioanal. Nucl. Chem.
DOI 10.1007/s10967-014-3911-6.
[6] M. Fellner, R.P. Baum, V. Kubícek, P. Hermann, I. Lukeš, V. Prasad et
al., “PET/CT imaging of osteoblastic bone metastases with 68Gabisphosphonates:
first human study,” Eur. J. Nucl. Med. Mol. Imaging,
vol. 37, pp. 834, 2010.
[7] J. Lai, S.M. Quadri, P.E. Borchardt, L. Harris , R. Wucher , E. Askew et
al., “Pharmaco-kinetics of radiolabeled polyclonal antiferritin in patients
with Hodgkin’s disease,” Clin. Cancer Res, vol. 5, pp. 3315−23, 1999.
[8] M.W. Nijhof, W.J. Oyen, A. Van Kampen, R.A. Claessens, J.W. Van
der Meer, F.H. Corstens, “Evaluation of infections of the locomotor
system with indium-111-labeled human IgG scintigraphy,” J. Nucl.
Med., vol. 38, pp. 1300−05, 1997.
[9] M.G. Stabin, M. Tagesson, S.R. Thomas, M. Ljungberg , S.E .Strand,
“Radiation dosimetry in nuclear medicine,” Appl. Radiat. Isot., vol. 50,
pp. 73-87, 1996.
[10] M.G. Stabin, “Internal Dosimetry in Nuclear Medicine,” Braz. J. Radiat.
Sci., vol. 01, pp. 1-15, 2013.
[11] M.G. Stabin, J.A. Siegel, “Physical Models and Dose Factors for Use in
Internal Dose Assessment,” Health. Phys., vol. 85, pp. 294-310, 2003.
[12] IAEA-TECDOC-1401, “Quantifying uncertainty in nuclear analytical
measurements,” Austria, Vienna: IAEA; 2004.
[13] R.B. Sparks, B. Aydogan, “Comparison of the effectiveness of some
common animal data scaling techniques in estimating human radiation
dose,” Sixth International Radiopharmaceutical Dosimetry Symposium,
Oak Ridge, TN: Oak Ridge Associated Universities, pp. 705–16, 1996.
[14] H. Yousefnia, S. Zolghadri, A.R. Jalilian, M. Tajik, M. Ghannadi-
Maragheh, “Preliminary dosimetric evaluation of 166Ho-TTHMP for
human based on biodistribution data in rats,” Appl. Radiat. Isot., vol. 94,
pp. 260-5, 2014.
[15] J.J. Bevelacqua, “Internal dosimetry primer,” Radiat. Prot. Manage., vol.
22, pp. 7-17, 2005.
[16] D.J. Brenner, “Effective dose: a flawed concept that could and should be
replaced,” British. J. Radiol., vol. 81, pp. 521–3, 2008.
[17] ICRP Publication 103, “The 2007 Recommendations of the International
Commission on Radiological Protection,” Ann. ICRP, vol. 37, pp. 2-4,
2007.
[18] United States Pharmacopoeia 28, NF 23, pp. 1009, 2005.
[19] J.T. Bushberg, J.A. Seibert, E.M. Leidholdt, J.M. Boone, “The Essential
Physics of Medical Imaging,” Third Edition, Lippincott Williams &
Wilkins; 2011.
[20] C. Muller, R. Schibli, “Single Photon Emission Computed Tomography
Tracer,” Mol. Imaging Oncol., vol. 187, pp. 65-105. 2013.
[21] A.L. Kesner, W.A. Hsueh, J. Czernin, H. Padgett, M.E. Phelps, D.H.
Silverman, “Radiation dose estimates for (18F)5-fluorouracil derived
from PET-based and tissue-based methods in rats,” Mol. Imaging Biol.,
vol. 10, pp. 341-8, 2008.
[22] ICRP Publication 62, “Radiological Protection in Biomedical Research,”
Ann. ICRP, vol. 22, pp. 3, 1993.
[23] ICRP Publication 53, “Radiation Dose to Patients from
Radiopharmaceuticals,” Ann. ICRP, vol. 18, pp. 1-4, 1988.
[24] Radiation Internal Dose Information Center, “Radiation dose estimates
to adults and children from various radiopharmaceuticals,” Oak Ridge
Institute for Science and Education. Oak Ridge, TN 37831. Available at:
orise.orau.gov/files/reacts/pedose.pdf.
[1] IAEA-TECDOC-1549, “Criteria for Palliation of Bone Metastases-
Clinical Applications,”. Austria, Vienna: IAEA; 2007.
[2] A. Lipton, “Pathophysiology of Bone Metastases: How This Knowledge
May Lead to Therapeutic Intervention,” J. Support. Oncol. vol. 2, pp.
205-20, 2004.
[3] M. Fellner, B. Biesalski, N. Bausbacher, V. Kubícek, P. Hermann, F.
Rösch, O. Thews, “68Ga-BPAMD: PET-imaging of bone metastases with
a generator based positron emitter,” Nucl. Med. Biol. vol. 39, pp. 993–9,
2012.
[4] G. Zettinig, T. Leitha, B. Niederle, K. Kaserer, A. Becherer, K. Kletter.
et al. “FDG positron emission tomographic, radioiodine, and MIBI
imaging in a patient with poorly differentiated insular thyroid
carcinoma,” Clin. Nucl. Med. Vol. 26, pp. 599–601, 2001.
[5] H. Yousefnia, A.R. Jalilian, S. Zolghadri, A. Mirzaei, A. Bahrami-
Samani, M. Mirzaii, M. Ghannadi, “Development of 111In DOTMP for
dosimetry of bone pain palliation agents,” J. Radioanal. Nucl. Chem.
DOI 10.1007/s10967-014-3911-6.
[6] M. Fellner, R.P. Baum, V. Kubícek, P. Hermann, I. Lukeš, V. Prasad et
al., “PET/CT imaging of osteoblastic bone metastases with 68Gabisphosphonates:
first human study,” Eur. J. Nucl. Med. Mol. Imaging,
vol. 37, pp. 834, 2010.
[7] J. Lai, S.M. Quadri, P.E. Borchardt, L. Harris , R. Wucher , E. Askew et
al., “Pharmaco-kinetics of radiolabeled polyclonal antiferritin in patients
with Hodgkin’s disease,” Clin. Cancer Res, vol. 5, pp. 3315−23, 1999.
[8] M.W. Nijhof, W.J. Oyen, A. Van Kampen, R.A. Claessens, J.W. Van
der Meer, F.H. Corstens, “Evaluation of infections of the locomotor
system with indium-111-labeled human IgG scintigraphy,” J. Nucl.
Med., vol. 38, pp. 1300−05, 1997.
[9] M.G. Stabin, M. Tagesson, S.R. Thomas, M. Ljungberg , S.E .Strand,
“Radiation dosimetry in nuclear medicine,” Appl. Radiat. Isot., vol. 50,
pp. 73-87, 1996.
[10] M.G. Stabin, “Internal Dosimetry in Nuclear Medicine,” Braz. J. Radiat.
Sci., vol. 01, pp. 1-15, 2013.
[11] M.G. Stabin, J.A. Siegel, “Physical Models and Dose Factors for Use in
Internal Dose Assessment,” Health. Phys., vol. 85, pp. 294-310, 2003.
[12] IAEA-TECDOC-1401, “Quantifying uncertainty in nuclear analytical
measurements,” Austria, Vienna: IAEA; 2004.
[13] R.B. Sparks, B. Aydogan, “Comparison of the effectiveness of some
common animal data scaling techniques in estimating human radiation
dose,” Sixth International Radiopharmaceutical Dosimetry Symposium,
Oak Ridge, TN: Oak Ridge Associated Universities, pp. 705–16, 1996.
[14] H. Yousefnia, S. Zolghadri, A.R. Jalilian, M. Tajik, M. Ghannadi-
Maragheh, “Preliminary dosimetric evaluation of 166Ho-TTHMP for
human based on biodistribution data in rats,” Appl. Radiat. Isot., vol. 94,
pp. 260-5, 2014.
[15] J.J. Bevelacqua, “Internal dosimetry primer,” Radiat. Prot. Manage., vol.
22, pp. 7-17, 2005.
[16] D.J. Brenner, “Effective dose: a flawed concept that could and should be
replaced,” British. J. Radiol., vol. 81, pp. 521–3, 2008.
[17] ICRP Publication 103, “The 2007 Recommendations of the International
Commission on Radiological Protection,” Ann. ICRP, vol. 37, pp. 2-4,
2007.
[18] United States Pharmacopoeia 28, NF 23, pp. 1009, 2005.
[19] J.T. Bushberg, J.A. Seibert, E.M. Leidholdt, J.M. Boone, “The Essential
Physics of Medical Imaging,” Third Edition, Lippincott Williams &
Wilkins; 2011.
[20] C. Muller, R. Schibli, “Single Photon Emission Computed Tomography
Tracer,” Mol. Imaging Oncol., vol. 187, pp. 65-105. 2013.
[21] A.L. Kesner, W.A. Hsueh, J. Czernin, H. Padgett, M.E. Phelps, D.H.
Silverman, “Radiation dose estimates for (18F)5-fluorouracil derived
from PET-based and tissue-based methods in rats,” Mol. Imaging Biol.,
vol. 10, pp. 341-8, 2008.
[22] ICRP Publication 62, “Radiological Protection in Biomedical Research,”
Ann. ICRP, vol. 22, pp. 3, 1993.
[23] ICRP Publication 53, “Radiation Dose to Patients from
Radiopharmaceuticals,” Ann. ICRP, vol. 18, pp. 1-4, 1988.
[24] Radiation Internal Dose Information Center, “Radiation dose estimates
to adults and children from various radiopharmaceuticals,” Oak Ridge
Institute for Science and Education. Oak Ridge, TN 37831. Available at:
orise.orau.gov/files/reacts/pedose.pdf.
@article{"International Journal of Medical, Medicine and Health Sciences:71311", author = "H. Yousefnia and S. Zolghadri", title = "Estimated Human Absorbed Dose of 111In-BPAMD as a New Bone-Seeking SPECT-Imaging Agent", abstract = "An early diagnosis of bone metastasis is very
important for making a right decision on a subsequent therapy. One
of the most important steps to be taken initially, for developing a new
radiopharmaceutical is the measurement of organ radiation exposure
dose. In this study, the dosimetric studies of a novel agent for
SPECT-imaging of the bone metastasis, 111In-(4-
{[(bis(phosphonomethyl))carbamoyl]methyl}7,10bis(carboxymethyl)
-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (111In-BPAMD)
complex, have been carried out to estimate the dose in human organs
based on the data derived from mice. The radiolabeled complex was
prepared with high radiochemical purity in the optimal conditions.
Biodistribution studies of the complex was investigated in the male
Syrian mice at the selected times after injection (2, 4, 24 and 48 h).
The human absorbed dose estimation of the complex was made based
on data derived from the mice by the radiation absorbed dose
assessment resource (RADAR) method. 111In-BPAMD complex was prepared with high radiochemical
purity >95% (ITLC) and specific activities of 2.85 TBq/mmol. Total
body effective absorbed dose for 111In-BPAMD was 0.205
mSv/MBq. This value is comparable to the other 111In clinically used
complexes. The results show that the dose with respect to the critical
organs is satisfactory within the acceptable range for diagnostic
nuclear medicine procedures. Generally, 111In-BPAMD has
interesting characteristics and it can be considered as a viable agent
for SPECT-imaging of the bone metastasis in the near future.", keywords = "In-111, BPAMD, absorbed dose, RADAR.", volume = "9", number = "9", pages = "722-5", }