Human Absorbed Dose Estimation of a New IN-111 Imaging Agent Based on Rat Data
The measurement of organ radiation exposure dose is
one of the most important steps to be taken initially, for developing a
new radiopharmaceutical. In this study, the dosimetric studies of a
novel agent for SPECT-imaging of the bone metastasis, 111In-
1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic
acid (111In-DOTMP) complex, have been carried out to estimate the
dose in human organs based on the data derived from rats. The
radiolabeled complex was prepared with high radiochemical purity in
the optimal conditions. Biodistribution studies of the complex was
investigated in the male Syrian rats at 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 rats by the
radiation absorbed dose assessment resource (RADAR) method.
111In-DOTMP complex was prepared with high radiochemical purity
of >99% (ITLC). Total body effective absorbed dose for 111In-
DOTMP was 0.061 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-
DOTMP has interesting characteristics and 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] L. D. Rybak, D. I. Rosenthal, "Radiological imaging for the diagnosis of
bone metastases," Q. J. Nucl. Med., vol. 45, pp. 53-64, 2001.
[4] Z.C. Traill, D. Talbot, S. Golding, F.V. Gleeson, "Magnetic resonance
imaging versus radionuclide scintigraphy in screening for bone
metastases," Clin. Radiol, vol. 54, pp. 448-51, 1999.
[5] 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.
[6] 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.
[7] Zh. Zhou, N.K. Wagh, S.M. Ogbomo, W. Shi, Y. Jia, S.K. Brusnahan et
al., "Synthesis and In Vitro and In Vivo Evaluation of Hypoxia-
Enhanced 111In-Bombesin Conjugates for Prostate Cancer Imaging., J.
Nucl. Med., vol. 54, pp. 1605-12, 2013.
[8] 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.
[9] 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.
[10] 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.
[11] M. G. Stabin, “Internal Dosimetry in Nuclear Medicine,” Braz. J. Radiat.
Sci., vol. 01, pp. 1-15, 2013.
[12] 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.
[13] IAEA-TECDOC-1401, “Quantifying uncertainty in nuclear analytical
measurements,” Austria, Vienna: IAEA; 2004.
[14] 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.
[15] 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.
[16] J.J. Bevelacqua, “Internal dosimetry primer,” Radiat. Prot. Manage., vol.
22, pp. 7-17, 2005.
[17] D. J. Brenner, “Effective dose: a flawed concept that could and should
be replaced,” British. J. Radiol., vol. 81, pp. 521–3, 2008.
[18] ICRP Publication 103, “The 2007 Recommendations of the International
Commission on Radiological Protection,” Ann. ICRP, vol. 37, pp. 2-4,
2007.
[19] United States Pharmacopoeia 28, NF 23, pp. 1009, 2005.
[20] United States Pharmacopoeia 28, NF 23, pp. 1895, 2005.
[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. pp. 14, 1996.
[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] L. D. Rybak, D. I. Rosenthal, "Radiological imaging for the diagnosis of
bone metastases," Q. J. Nucl. Med., vol. 45, pp. 53-64, 2001.
[4] Z.C. Traill, D. Talbot, S. Golding, F.V. Gleeson, "Magnetic resonance
imaging versus radionuclide scintigraphy in screening for bone
metastases," Clin. Radiol, vol. 54, pp. 448-51, 1999.
[5] 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.
[6] 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.
[7] Zh. Zhou, N.K. Wagh, S.M. Ogbomo, W. Shi, Y. Jia, S.K. Brusnahan et
al., "Synthesis and In Vitro and In Vivo Evaluation of Hypoxia-
Enhanced 111In-Bombesin Conjugates for Prostate Cancer Imaging., J.
Nucl. Med., vol. 54, pp. 1605-12, 2013.
[8] 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.
[9] 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.
[10] 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.
[11] M. G. Stabin, “Internal Dosimetry in Nuclear Medicine,” Braz. J. Radiat.
Sci., vol. 01, pp. 1-15, 2013.
[12] 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.
[13] IAEA-TECDOC-1401, “Quantifying uncertainty in nuclear analytical
measurements,” Austria, Vienna: IAEA; 2004.
[14] 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.
[15] 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.
[16] J.J. Bevelacqua, “Internal dosimetry primer,” Radiat. Prot. Manage., vol.
22, pp. 7-17, 2005.
[17] D. J. Brenner, “Effective dose: a flawed concept that could and should
be replaced,” British. J. Radiol., vol. 81, pp. 521–3, 2008.
[18] ICRP Publication 103, “The 2007 Recommendations of the International
Commission on Radiological Protection,” Ann. ICRP, vol. 37, pp. 2-4,
2007.
[19] United States Pharmacopoeia 28, NF 23, pp. 1009, 2005.
[20] United States Pharmacopoeia 28, NF 23, pp. 1895, 2005.
[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. pp. 14, 1996.
@article{"International Journal of Engineering, Mathematical and Physical Sciences:71268", author = "H. Yousefnia and S. Zolghadri", title = "Human Absorbed Dose Estimation of a New IN-111 Imaging Agent Based on Rat Data", abstract = "The measurement of organ radiation exposure dose is
one of the most important steps to be taken initially, for developing a
new radiopharmaceutical. In this study, the dosimetric studies of a
novel agent for SPECT-imaging of the bone metastasis, 111In-
1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraethylene phosphonic
acid (111In-DOTMP) complex, have been carried out to estimate the
dose in human organs based on the data derived from rats. The
radiolabeled complex was prepared with high radiochemical purity in
the optimal conditions. Biodistribution studies of the complex was
investigated in the male Syrian rats at 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 rats by the
radiation absorbed dose assessment resource (RADAR) method.
111In-DOTMP complex was prepared with high radiochemical purity
of >99% (ITLC). Total body effective absorbed dose for 111In-
DOTMP was 0.061 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-
DOTMP has interesting characteristics and can be considered as a
viable agent for SPECT-imaging of the bone metastasis in the near
future.", keywords = "In-111, DOTMP, Internal Dosimetry, RADAR.", volume = "9", number = "10", pages = "616-5", }
