Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis
[en] Purpose: Many anticancer therapies exert their therapeutic effect by inducing apoptosis in target tumors. We evaluated in a Phase I study the safety and the feasibility of Tc-99m-Annexin V for imaging chemotherapy-induced apoptosis in human cancers immediately after the first course of chemotherapy. Experimental Design: Fifteen patients presenting with lung cancer (n = 10), lymphoma (n = 3), or breast cancer (n = 2) underwent Tc-99m-Annexin V scintigraphy before and within 3 days after their first course of chemotherapy. Tumor response was evaluated by computed tomography and F-18-fluoro-2-deoxy-D-glucose positron emission tomography scans, 3 months in average after completing the treatment. Median follow-up was 117 days. Results: In all cases, no tracer uptake was observed before treatment. However, 24-48 h after the first course of chemotherapy, 7 patients who showed Tc-99m-Annexin V uptake at tumor sites, suggesting apoptosis, had a complete (n = 4) or a partial response In = 3). Conversely, 6 of the 8 patients who showed no significant posttreatment tumor uptake had a progressive disease. Despite the lack of tracer uptake after treatment, the 2 patients with breast cancer had a partial response. Overall survival and progression-free survival were significantly related to tracer uptake in treated lung cancers and lymphomas (P < 0.05). No serious adverse events were observed. Conclusions: Our preliminary results demonstrated the feasibility and the safety of Tc-99m-Annexin V for imaging apoptosis in human tumors after the first course of chemotherapy. Initial data suggest that early Tc-99m-Annexin V tumor uptake may be a predictor of response to treatment in-patients with late stage lung cancer and lymphoma.
Disciplines :
Oncology
Author, co-author :
Belhocine, Tarik
Steinmetz, Neil
Hustinx, Roland ; Université de Liège - ULiège > Département des sciences cliniques > Médecine nucléaire
Bartsch, Pierre ; Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > Oncologie médicale
Seidel, Laurence ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Rigo, Pierre ; Université de Liège - ULiège > Département des sciences de la motricité > Pathologie générale et médecine nucléaire
Green, Allan
Language :
English
Title :
Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis
Publication date :
September 2002
Journal title :
Clinical Cancer Research
ISSN :
1078-0432
eISSN :
1557-3265
Publisher :
American Association for Cancer Research, Inc. (AACR)
Kerr J.F., Wyllie A.H., Currie A.R. (1972) Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26:239-257.
Evan G.I., Vousden K.H. (2001) Proliferation, cell cycle, and apoptosis in cancer. Nature (Lond.) 411:342-348.
Harrington E.A., Fanidi A., Evan G.I. (1994) Oncogenes and cell death. Curr. Opin. Genet. Dev. 4:120-129.
Darzynkiewicz Z. (1995) Apoptosis in antitumor strategies: Modulation of cell cycle or differentiation. J. Cell. Biochem. 58:151-159.
Lennon S.V., Martin S.J., Cotter T.G. (1991) Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Prolif. 24:203-214.
Martin S.J., Reutelingsperger C.P., McGahon A.J., Rader J.A., Van Schie R.C., LaFace D.M., Green D.R. (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: Inhibition by over expression of Bcl-2 and Ab1. J. Exp. Med. 182:1545-1556.
Ogura Y., Krams S.M., Martinez O.M., Kopiwoda S., Higgins J.P., Esquivel C.O., Strauss H.W., Tait J.F., Blankenberg F.G. (2000) Radiolabeled annexin V imaging: Diagnosis of allograft rejection in an experimental rodent model of liver transplantation. Radiology 214:795-800.
Vriens P.W., Blankenberg F.G., Stoot J.H., Ohtsuki K., Berry G.J., Tait J.F., Strauss H.W., Robbins R.C. (1998) The use of technetium Tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection. J. Thorac. Cardiovasc. Surg. 116:844-853.
Blankenberg F.G., Robbins R.C., Stoot J.H., Vriens P.W., Berry G.J., Tait J.F., Strauss H.W. (2000) Radionucleide imaging of acute lung transplant rejection with annexin V. Chest 117:834-840.
Blankenberg F.G., Ohtsuki K., Tait J., Strauss H.W. (2000) Apoptosis: The importance of nuclear medicine. Nucl. Med. Commun. 21:241-250.
Ohtsuki K., Akashi K., Aoka Y., Blankenberg F.G., Kopiwoda S., Tait J.F., Strauss H.W. (1999) Technetium-99m HYNIC-annexin V: A potential radiopharmaceutical for the in vivo detection of apoptosis. Eur. J. Nucl. Med. 26:1251-1258.
Blankenberg F.G., Katsikis P.D., Tait F., Davis R.E., Naumovski L., Ohtsuki K., Kopiwoda S., Abrams M.J., Strauss H.W. (1999) Imaging of apoptosis (programmed cell death) with 99mTc annexin V. J. Nucl. Med. 40:184-191.
D'Arceuil H., Rhine W., De Crespigny A., Yenari M., Tait J.F., Strauss W.H., Engelhorn T., Kastrup A., Moseley M., Blankenberg F.G. (2000) 99mTc annexin V imaging of neonatal hypoxic brain injury. Stroke 31:2692-2700.
Blankenberg F.G., Naumovski L., Tait J.F., Post A.M., Strauss H.W. (2001) Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V. J. Nucl. Med. 42:309-316.
Hofstra L., Liem I.H., Dumont E.A., Boersma H.H., Van Heerde W.L., Doevendans P.A., De Muinck E., Wellens H.J., Kemerink G.J., Reutelingsperger C.P., Heidendal G.A. (2000) Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet 356:209-212.
Narula J., Acio E.R., Narula N., Samuels L.E., Fyfe B., Wood D., Fitzpatrick J.M., Raghunath P.N., Tomaszewski J.E., Kelly C., Steinmetz N., Green A., Tait J.F., Leppo J., Blankenberg F.G., Jain D., Strauss H.W. (2001) Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat. Med. 7:1347-1352.
Zwaal R.F., Schroit A.J. (1997) Pathophysiologic implications of membrane phopholipid asymmetry in blood cells. Blood 89:1121-1132.
Cookson B.T., Engelhardt S., Smith C., Bamford H.A., Prochazka M., Tait J.F. (1994) Organization of the human annexin V (ANX5) gene. Genomics 20:463-467.
Huber R., Berendes R., Burger A., Schneider M., Karshikov A., Luecke H., Romisch J., Pâques E. (1992) Crystal and molecular structure of human annexin V after refinement. Implications for structure, membrane binding and ion channel formation of the annexin family of proteins. J. Mol. Biol. 223:683-704.
Pigault C., Follenius-Wund A., Schmutz M., Freyssinet J.M., Brisson A. (1994) Formation of two-dimensional arrays of annexin V on phosphatidylserine-containing liposomes. J. Mol. Biol. 236:199-208.
Meers P., Mealy T. (1993) Relationship between annexin V tryptophan exposure, calcium, and phospholipid binding. Biochemistry 32:5411-5418.
Kasina S., Rao T.N., Srinivasan A., Sanderson J.A., Fitzner J.N., Reno J.M., Beaumier P.L., Fritzberg A.R. (1991) Development and biologic evaluation of a kit for preformed chelate technetium-99m radiolabeling of an antibody Fab fragment using a diamide dimercaptide chelating agent. J. Nucl. Med. 32:1445-1451.
Hickman J.A. (1992) Apoptosis induced by anticancer drugs. Cancer Metastasis Rev. 11:121-139.
Dive C., Evans C.A., Whetton A.D. (1992) Induction of apoptosis: New targets for cancer chemotherapy. Semin. Cancer Biol. 3:417-427.
Lowe S.W., Lin A.W. (2000) Apoptosis in cancer. Carcinogenesis (Lond.) 21:485-495.
Murakami Y., Hayashi K., Hirohashi S., Sekiya T. (1991) Aberrations of the tumor suppressor p 53 and retinoblastoma genes in human hepatocellular carcinomas. Cancer Res. 51:5520-5525.
Lowe S.W. (1995) Cancer therapy and p53. Curr. Opin. Oncol. 7:547-553.
Weiss L.M., Warnke R.A., Sklar J., Cleary M.L. (1987) Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N. Engl. J. Med. 317:1185-1189.
Vaux D.L., Cory S., Adams J.M. (1988) Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature (Lond.) 335:440-442.
Maloney D.G., Smith B., Appelbaum F.R. (1996) The anti-tumor effect of monoclonal anti-CD20 antibody therapy includes direct anti-proliferative activity and induction of apoptosis in CD20 positive non-Hodgkin's lymphoma cell lines. Blood 88:637a.
Demidem A., Lam T., Alas S., Hariharan K., Hanna N., Bonavida B. (1997) Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother. Radiopharm. 12:177-186.
Ghosh M., Crocker J., Morris A. (2001) Apoptosis in squamous cell carcinoma of the lung: Correlation with survival and clinicopathological features. J. Clin. Pathol. 54:111-115.
Gonzalez-Palacios F., Sancho M., Martinez J.C., Bellas C. (1997) Microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma. Mol. Pathol. 50:304-309.
Allen R.T., Hunter W.J., Agrawal D.K. (1997) Morphological and biochemistry characterization and analysis of apoptosis. J. Pharmacol. Toxicol. Meth. 37:215-228.
Warburg O. (1956) On the origin of cancer cells. Science (Wash. DC) 123:309-314.
Pauwels E.K., Ribeiro M.J., Stoot J.H., McCready V.R., Bourguignon M., Maziere B. (1998) FDG accumulation and tumor biology. Nucl. Med. Biol. 25:317-322.
Delbeke D. (1999) Oncological applications of FDG PET imaging. J. Nucl. Med. 40:1706-1715.
Bar-Shalom R., Valdivia A.Y., Blaufox M.D. (2000) PET imaging in oncology. Semin. Nucl. Med. 30:150-185.