Skip to main content
Top
Published in: Molecular Imaging and Biology 2/2009

01-03-2009 | Research Article

Imaging and Pharmacokinetics of 64Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin’s Lymphoma Xenografts

Authors: Shiloh M. Martin, Robert T. O’Donnell, David L. Kukis, Craig K. Abbey, Hayes McKnight, Julie L. Sutcliffe, Joseph M. Tuscano

Published in: Molecular Imaging and Biology | Issue 2/2009

Login to get access

Abstract

Purpose

The aim of the study is to compare the tumor-specific targeting, pharmacokinetics, and biodistribution of 64Cu-DOTA-HB22.7 when administered to xenograft-bearing mice intravenously (IV), intraperitoneally (IP), and subcutaneously (SQ).

Procedures

Mice bearing human non-Hodgkin’s lymphoma (NHL) xenografts were injected IV, IP, or SQ with 64Cu-DOTA-HB22.7. Xenograft targeting was evaluated by micro positron emission tomography (microPET) and confirmed by organ biodistribution studies. Blood measurements of 64Cu were performed to determine the pharmacokinetics and clearance of 64Cu-DOTA-HB22.7.

Results

64Cu-DOTA-HB22.7 demonstrated equivalent tumor targeting within 24–48 h, regardless of the route of administration. Organ biodistribution confirmed tumor-specific targeting. Blood pharmacokinetics demonstrated that 64Cu-DOTA-HB22.7 accessed the bloodstream after IP and SQ administration to a similar degree as IV administration, albeit at a slower rate.

Conclusions

These findings establish 64Cu-DOTA-HB22.7 as a potential radioimmunotherapeutic and/or NHL-specific imaging agent. These findings provide evidence that IP and SQ administration can achieve results equivalent to IV administration and may lead to more efficient, reproducible treatment plans for antibody-based therapeutics.
Literature
1.
go back to reference Schumer ST, Joyce RM (2003) Radioimmunotherapy for Non-Hodgkin’s Lymphoma. Progress in Oncology 46–72 Schumer ST, Joyce RM (2003) Radioimmunotherapy for Non-Hodgkin’s Lymphoma. Progress in Oncology 46–72
2.
go back to reference Lindley C (1991) The lymphomas: Hodgkin’s disease and non-Hodgkin’s lymphomas. Am Pharm NS31 46–51 Lindley C (1991) The lymphomas: Hodgkin’s disease and non-Hodgkin’s lymphomas. Am Pharm NS31 46–51
3.
go back to reference DeNardo GL (2005) Treatment of non-Hodgkin’s lymphoma (NHL) with radiolabeled antibodies (mAbs). Semin Nucl Med 35:202–211PubMedCrossRef DeNardo GL (2005) Treatment of non-Hodgkin’s lymphoma (NHL) with radiolabeled antibodies (mAbs). Semin Nucl Med 35:202–211PubMedCrossRef
4.
go back to reference DeNardo GL, O'Donnell RT, DeNardo SJ (2001) Radiolabeled anti-lymphoma antibodies. Cancer Chemother Biol Response Modif 19:297–308PubMed DeNardo GL, O'Donnell RT, DeNardo SJ (2001) Radiolabeled anti-lymphoma antibodies. Cancer Chemother Biol Response Modif 19:297–308PubMed
5.
go back to reference Kukis DL, DeNardo GL, DeNardo SJ et al (1995) Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. Cancer Res 55:878–884PubMed Kukis DL, DeNardo GL, DeNardo SJ et al (1995) Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. Cancer Res 55:878–884PubMed
6.
go back to reference Juweid ME (2002) Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma: from clinical trials to clinical practice. J Nucl Med 43:1507–1529PubMed Juweid ME (2002) Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma: from clinical trials to clinical practice. J Nucl Med 43:1507–1529PubMed
7.
go back to reference Riley MB, Gordon LI (2004) Efficacy and safety of radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin). Semin Oncol Nurs 20:8–13PubMedCrossRef Riley MB, Gordon LI (2004) Efficacy and safety of radioimmunotherapy with yttrium 90 ibritumomab tiuxetan (Zevalin). Semin Oncol Nurs 20:8–13PubMedCrossRef
8.
go back to reference Hjortland GO, Garman-Vik SS, Juell S (2004) Immunotoxin treatment targeted to the high-molecular-weight melanoma-associated antigen prolonging the survival of immunodeficient rats with invasive intracranial human glioblastoma multiforme. J Neurosurg 100:320–327PubMed Hjortland GO, Garman-Vik SS, Juell S (2004) Immunotoxin treatment targeted to the high-molecular-weight melanoma-associated antigen prolonging the survival of immunodeficient rats with invasive intracranial human glioblastoma multiforme. J Neurosurg 100:320–327PubMed
9.
go back to reference Kawakami K, Nakajima O, Morishita R, Nagai R (2006) Targeted anticancer immunotoxins and cytotoxic agents with direct killing moieties. Scientific World Journal 6:781–790PubMed Kawakami K, Nakajima O, Morishita R, Nagai R (2006) Targeted anticancer immunotoxins and cytotoxic agents with direct killing moieties. Scientific World Journal 6:781–790PubMed
10.
go back to reference Tedder TF, Tuscano J, Sato S, Kehrl JH (1997) CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Annu Rev Immunol 15:481–504PubMedCrossRef Tedder TF, Tuscano J, Sato S, Kehrl JH (1997) CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Annu Rev Immunol 15:481–504PubMedCrossRef
11.
go back to reference Sato S, Tuscano JM, Inaoki M, Tedder TF (1998) CD22 negatively and positively regulates signal transduction through the B lymphocyte antigen receptor. Semin Immunol 10:287–297PubMedCrossRef Sato S, Tuscano JM, Inaoki M, Tedder TF (1998) CD22 negatively and positively regulates signal transduction through the B lymphocyte antigen receptor. Semin Immunol 10:287–297PubMedCrossRef
12.
go back to reference Tuscano JM, Riva A, Toscano SN, Tedder TF, Kehrl JH (1999) CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. Blood 94:1382–1392PubMed Tuscano JM, Riva A, Toscano SN, Tedder TF, Kehrl JH (1999) CD22 cross-linking generates B-cell antigen receptor-independent signals that activate the JNK/SAPK signaling cascade. Blood 94:1382–1392PubMed
13.
go back to reference Tuscano JM, O'Donnell RT, Miers LA et al (2003) Anti-CD22 ligand-blocking antibody HB22.7 has independent lymphomacidal properties and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma xenografts. Blood 101:3641–3647PubMedCrossRef Tuscano JM, O'Donnell RT, Miers LA et al (2003) Anti-CD22 ligand-blocking antibody HB22.7 has independent lymphomacidal properties and augments the efficacy of 90Y-DOTA-peptide-Lym-1 in lymphoma xenografts. Blood 101:3641–3647PubMedCrossRef
14.
go back to reference Koppe MJ, Postema EJ, Aarts F, Oyen WJ, Bleichrodt RP, Boerman OC (2005) Antibody-guided radiation therapy of cancer. Cancer Metastasis Rev 24:539–567PubMedCrossRef Koppe MJ, Postema EJ, Aarts F, Oyen WJ, Bleichrodt RP, Boerman OC (2005) Antibody-guided radiation therapy of cancer. Cancer Metastasis Rev 24:539–567PubMedCrossRef
15.
go back to reference Postema EJ, Boerman OC, Oyen WJ, Raemaekers JM, Corstens FH (2001) Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma. Eur J Nucl Med 28:1725–1735PubMedCrossRef Postema EJ, Boerman OC, Oyen WJ, Raemaekers JM, Corstens FH (2001) Radioimmunotherapy of B-cell non-Hodgkin’s lymphoma. Eur J Nucl Med 28:1725–1735PubMedCrossRef
16.
go back to reference O'Grady LF, DeNardo G, DeNardo S (1986) Radiolabelled monoclonal antibodies for the detection of cancer. Am J Physiol Imaging 1:44–53PubMed O'Grady LF, DeNardo G, DeNardo S (1986) Radiolabelled monoclonal antibodies for the detection of cancer. Am J Physiol Imaging 1:44–53PubMed
17.
go back to reference Rao AV, Akabani G, Rizzieri DA (2005) Radioimmunotherapy for Non-Hodgkin’s Lymphoma. Clin Med Res 3:157–165PubMedCrossRef Rao AV, Akabani G, Rizzieri DA (2005) Radioimmunotherapy for Non-Hodgkin’s Lymphoma. Clin Med Res 3:157–165PubMedCrossRef
19.
go back to reference Phelps ME (2000) Inaugural article: positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci USA 97:9226–9233PubMedCrossRef Phelps ME (2000) Inaugural article: positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci USA 97:9226–9233PubMedCrossRef
20.
go back to reference Winnard P Jr., Raman V (2003) Real time non-invasive imaging of receptor-ligand interactions in vivo. J Cell Biochem 90:454–463PubMedCrossRef Winnard P Jr., Raman V (2003) Real time non-invasive imaging of receptor-ligand interactions in vivo. J Cell Biochem 90:454–463PubMedCrossRef
21.
go back to reference Hale G, Rebello P, Brettman LR et al (2004) Blood concentrations of alemtuzumab and antiglobin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration. Blood 104:948–955PubMedCrossRef Hale G, Rebello P, Brettman LR et al (2004) Blood concentrations of alemtuzumab and antiglobin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration. Blood 104:948–955PubMedCrossRef
22.
go back to reference Meares CF, McCall MJ, Reardan DT, Goodwin DA, Diamanti CI, McTigue M (1984) Conjugation of antibodies with bifunctional chelating agents: isothiocyanate and bromoacetamide reagents, methods of analysis, and subsequent addition of metal ions. Anal Biochem 142:68–78PubMedCrossRef Meares CF, McCall MJ, Reardan DT, Goodwin DA, Diamanti CI, McTigue M (1984) Conjugation of antibodies with bifunctional chelating agents: isothiocyanate and bromoacetamide reagents, methods of analysis, and subsequent addition of metal ions. Anal Biochem 142:68–78PubMedCrossRef
23.
go back to reference McCarthy DW, Shefer RE, Klinkowstein RE et al (1997) Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl Med Biol 24:35–43PubMedCrossRef McCarthy DW, Shefer RE, Klinkowstein RE et al (1997) Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl Med Biol 24:35–43PubMedCrossRef
24.
go back to reference Tai YC, Chatziioannou AF, Yang Y et al (2003) MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging. Phys Med Biol 48:1519–1537PubMedCrossRef Tai YC, Chatziioannou AF, Yang Y et al (2003) MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging. Phys Med Biol 48:1519–1537PubMedCrossRef
25.
go back to reference Chatziioannou A, Tai YC, Doshi N, Cherry SR (2001) Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging. Phys Med Biol 46:2899–2910PubMedCrossRef Chatziioannou A, Tai YC, Doshi N, Cherry SR (2001) Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging. Phys Med Biol 46:2899–2910PubMedCrossRef
26.
go back to reference Qi J, Leahy RM, Cherry SR, Chatziioannou A, Farquhar TH (1998) High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner. Phys Med Biol 43:1001–1013PubMedCrossRef Qi J, Leahy RM, Cherry SR, Chatziioannou A, Farquhar TH (1998) High-resolution 3D Bayesian image reconstruction using the microPET small-animal scanner. Phys Med Biol 43:1001–1013PubMedCrossRef
27.
go back to reference Chatziioannou A, Qi J, Moore A et al (2000) Comparison of 3-D maximum a posteriori and filtered backprojection algorithms for high-resolution animal imaging with microPET. IEEE Trans Med Imaging 19:507–512PubMedCrossRef Chatziioannou A, Qi J, Moore A et al (2000) Comparison of 3-D maximum a posteriori and filtered backprojection algorithms for high-resolution animal imaging with microPET. IEEE Trans Med Imaging 19:507–512PubMedCrossRef
28.
go back to reference Abbey CK, Borowsky AD, McGoldrick ET et al (2004) In vivo positron-emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia. Proc Natl Acad Sci USA 101:11438–11443PubMedCrossRef Abbey CK, Borowsky AD, McGoldrick ET et al (2004) In vivo positron-emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia. Proc Natl Acad Sci USA 101:11438–11443PubMedCrossRef
29.
go back to reference Qi J, Leahy RM (1999) A theoretical study of the contrast recovery and variance of MAP reconstructions from PET data. IEEE Trans Med Imaging 18:293–305PubMedCrossRef Qi J, Leahy RM (1999) A theoretical study of the contrast recovery and variance of MAP reconstructions from PET data. IEEE Trans Med Imaging 18:293–305PubMedCrossRef
30.
go back to reference Love C, Tomas MB, Tronco GG, Palestro CJ (2005) FDG PET of infection and inflammation. Radiographics 25:1357–1368PubMedCrossRef Love C, Tomas MB, Tronco GG, Palestro CJ (2005) FDG PET of infection and inflammation. Radiographics 25:1357–1368PubMedCrossRef
31.
go back to reference Rosenbaum SJ, Lind T, Antoch G, Bockisch A (2006) False-positive FDG PET uptake—the role of PET/CT. Eur Radiol 16:1054–1065PubMedCrossRef Rosenbaum SJ, Lind T, Antoch G, Bockisch A (2006) False-positive FDG PET uptake—the role of PET/CT. Eur Radiol 16:1054–1065PubMedCrossRef
32.
go back to reference Jacene HA, Stearns V, Wahl RL (2006) Lymphadenopathy resulting from acute hepatitis C infection mimicking metastatic breast carcinoma on FDG PET/CT. Clin Nucl Med 31:379–381PubMedCrossRef Jacene HA, Stearns V, Wahl RL (2006) Lymphadenopathy resulting from acute hepatitis C infection mimicking metastatic breast carcinoma on FDG PET/CT. Clin Nucl Med 31:379–381PubMedCrossRef
33.
go back to reference Engel P, Wagner N, Miller AS, Tedder TF (1995) Identification of the ligand binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand. J Exp Med 181:1581–1586PubMedCrossRef Engel P, Wagner N, Miller AS, Tedder TF (1995) Identification of the ligand binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand. J Exp Med 181:1581–1586PubMedCrossRef
34.
go back to reference Eischen A, Doclos B, Schmitt-Goguel M et al (1994) Human resident peritoneal macrophages: phenotype and biology. Br J Haematol 88:712–722PubMedCrossRef Eischen A, Doclos B, Schmitt-Goguel M et al (1994) Human resident peritoneal macrophages: phenotype and biology. Br J Haematol 88:712–722PubMedCrossRef
35.
go back to reference Whitelaw DM (1966) The intravascular lifespan of monocytes. Blood 28:455–464PubMed Whitelaw DM (1966) The intravascular lifespan of monocytes. Blood 28:455–464PubMed
36.
go back to reference Garner B, van Reyk D, Dean RT, Jessup W (1997) Direct copper reduction by macrophagesIts role in low density lipoprotein oxidation. J Biol Chem 272:6927–6935PubMedCrossRef Garner B, van Reyk D, Dean RT, Jessup W (1997) Direct copper reduction by macrophagesIts role in low density lipoprotein oxidation. J Biol Chem 272:6927–6935PubMedCrossRef
37.
go back to reference Ehrenwald E, Chisolm GM, Fox PL (1994) Intact human ceruloplasmin oxidatively modifies low density lipoprotein. J Clin Invest 93:1493–1501PubMedCrossRef Ehrenwald E, Chisolm GM, Fox PL (1994) Intact human ceruloplasmin oxidatively modifies low density lipoprotein. J Clin Invest 93:1493–1501PubMedCrossRef
38.
go back to reference Ehrenwald E, Fox PL (1996) Role of endogenous ceruloplasmin in low density lipoprotein oxidation by human U937 monocytic cells. J Clin Invest 97:884–890PubMedCrossRef Ehrenwald E, Fox PL (1996) Role of endogenous ceruloplasmin in low density lipoprotein oxidation by human U937 monocytic cells. J Clin Invest 97:884–890PubMedCrossRef
39.
go back to reference Chung J, Haile DJ, Wessling-Resnick M (2004) Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux. Proc Natl Acad Sci USA 101:2700–2705PubMedCrossRef Chung J, Haile DJ, Wessling-Resnick M (2004) Copper-induced ferroportin-1 expression in J774 macrophages is associated with increased iron efflux. Proc Natl Acad Sci USA 101:2700–2705PubMedCrossRef
40.
go back to reference Rossi F (1986) The O2 −-forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function. Biochim Biophys Acta 853:65–89PubMed Rossi F (1986) The O2 -forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function. Biochim Biophys Acta 853:65–89PubMed
41.
go back to reference Babior BM, Kipnes RS, Curnutte JT (1973) Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52:741–744PubMedCrossRef Babior BM, Kipnes RS, Curnutte JT (1973) Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest 52:741–744PubMedCrossRef
42.
go back to reference Pietarinen-Runtti P, Lakari E, Raivio KO, Kinnula VL (2000) Expression of antioxidant enzymes in human inflammatory cells. Am J Physiol Cell Physiol 278:C118–C125PubMed Pietarinen-Runtti P, Lakari E, Raivio KO, Kinnula VL (2000) Expression of antioxidant enzymes in human inflammatory cells. Am J Physiol Cell Physiol 278:C118–C125PubMed
43.
go back to reference Grunberg J, Novak-Hofer I, Honer M et al (2005) In-vivo evaluation of 177Lu- and 67/64Cu-labeled recombinant fragments of antibody chCE7 for radioimmunotherapy and PET imaging of L1-CAM positive tumors. Clin Cancer Res 11:5112–5120PubMedCrossRef Grunberg J, Novak-Hofer I, Honer M et al (2005) In-vivo evaluation of 177Lu- and 67/64Cu-labeled recombinant fragments of antibody chCE7 for radioimmunotherapy and PET imaging of L1-CAM positive tumors. Clin Cancer Res 11:5112–5120PubMedCrossRef
44.
go back to reference Lewis MR, Boswell CA, Laforest R et al (2001) Conjugation of monoclonal antibodies with TETA using activated esters: biological comparison of 64Cu-TETA-1A3 with 64Cu-BAT-2IT-1A3. Cancer Biother Radiopharm 16:483–494PubMedCrossRef Lewis MR, Boswell CA, Laforest R et al (2001) Conjugation of monoclonal antibodies with TETA using activated esters: biological comparison of 64Cu-TETA-1A3 with 64Cu-BAT-2IT-1A3. Cancer Biother Radiopharm 16:483–494PubMedCrossRef
45.
go back to reference Cai W, Ebrahimnejad A, Chen K et al (2007) Quantitative radioimmunoPET imaging of EphA2 in tumor-bearing mice. Eur J Nucl Med Mol Imaging 34:2024–2036PubMedCrossRef Cai W, Ebrahimnejad A, Chen K et al (2007) Quantitative radioimmunoPET imaging of EphA2 in tumor-bearing mice. Eur J Nucl Med Mol Imaging 34:2024–2036PubMedCrossRef
46.
go back to reference DeNardo GL, DeNardo SJ, Meares CF et al (1991) Pharmacokinetics of copper-67 conjugated Lym-1, a potential therapeutic radioimmunoconjugate, in mice and in patients with lymphoma. Antibody Immunoconj Radiopharm 4:777–785 DeNardo GL, DeNardo SJ, Meares CF et al (1991) Pharmacokinetics of copper-67 conjugated Lym-1, a potential therapeutic radioimmunoconjugate, in mice and in patients with lymphoma. Antibody Immunoconj Radiopharm 4:777–785
47.
go back to reference Deshpande SV, DeNardo SJ, Meares CF et al (1988) Copper-67-labeled monoclonal antibody Lym-1, a potential radiopharmaceutical for cancer therapy: labeling and biodistribution in Raji tumored mice. J Nucl Med 29:217–225PubMed Deshpande SV, DeNardo SJ, Meares CF et al (1988) Copper-67-labeled monoclonal antibody Lym-1, a potential radiopharmaceutical for cancer therapy: labeling and biodistribution in Raji tumored mice. J Nucl Med 29:217–225PubMed
Metadata
Title
Imaging and Pharmacokinetics of 64Cu-DOTA-HB22.7 Administered by Intravenous, Intraperitoneal, or Subcutaneous Injection to Mice Bearing Non-Hodgkin’s Lymphoma Xenografts
Authors
Shiloh M. Martin
Robert T. O’Donnell
David L. Kukis
Craig K. Abbey
Hayes McKnight
Julie L. Sutcliffe
Joseph M. Tuscano
Publication date
01-03-2009
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 2/2009
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-008-0148-1

Other articles of this Issue 2/2009

Molecular Imaging and Biology 2/2009 Go to the issue