Magnetically Targeted Microspheres for Intracavitary and Intraspinal Y-90 Radiotherapy
Targeted approaches to radiotherapy using long-range ß-emitting isotopes linked to biologically selective molecules such as antibodies have shown limited success, primarily due to the relatively small amounts of radioactive material that actually reach the tumor sites. Tissuecompatible magnetic microspheres, however, can incorporate very high concentrations of radioactive material and can be maneuvered within the body through the use of an external magnetic field like that generated by a clinical MRI machine. Magnetic microspheres (MMS), 10–30 gm in diameter, were prepared from poly (lactic acid) by a solvent-evaporation method, contained 30 weight% magnetite and were loaded shortly before injection with the ß-emitting radioisotope 90Y. This radiopharmaceutical was tested in vivo in two animal models. The results from the subcutaneous mouse lymphoma model are promising and show that the locally concentrated magnetic microspheres are able to eradicate more than half of the tumors. The results from an intraspinal glioblastoma model in rats, however, failed to show a significant difference between magnetically targeted radioactive microspheres and radioactive microspheres which had not been subjected to a magnetic field. Nonetheless, both groups of radioactively treated rats lived significantly longer than animals injected with non-radioactive microspheres. Higher magnetic fields and field gradients and more susceptible, smaller magnetic microspheres might be required to achieve intraspinal magnetic targeting.
KeywordsLactic Acid Magnetic Field Gradient Magnetic Microsphere NdFeB Magnet Magnetic Target
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Gupta PK and Hung CT (1989).Magnetically controlled targeted micro-carrier systems.
Life Sci. 44
Jain RK (1991). Invited Review: Haemodvnamic and transport barriers to the treatment of solid tumours.
Int. J. Radial. Biol. 60
Clarke SEM (1994). Antitumor treatment: Radionuclide therapy in oncology.
Cancer Treat. Rev. 20
Allen BJ and Blagojevic N (1996). Alpha-and beta-emitting radiolanthanides in targeted cancer therapy: The potential role of terbium-149.
Nuclear Medicine Communications 17
Andrews JC, Walker SC, Ackermann Ri, et al (1994). Hepatic radioembolization with Yttrium-90 containing glass microspheres: Preliminary results and clinical follow up.
J. Nucl. Med. 35
Ehrhardt GJ and Day DE (1987). Therapeutic use of Y microspheres.
Nucl. Med. Biol. 14
Stucki G, Bozzone P, Treuer E, et al (1993). Efficacy and safety of radiation synovectomy with Yttrium-90: A retrospective long-term analysis of 164 applications in 82 patients.
Brit. J. Rheumatol. 32
Rowlinson G and Epenetos AA (1992). Targeted delivery of biologic and other antineoplastic agents.
Current Opinion in Oncology 4
Persaud RD (1988). Biting the magic bullet. Radiolabelled monoclonal antibodies: The next great step forward in the diagnosis and treatment of cancer
Medical Hypotheses 27
Bradley EW, Chan PC and Adelstein Si (1975). The radiotoxicity of iodine-125 in mammalian cells. Effects on the survival curve of radioiodine incorporated into DNA
. Radiat. Res. 64
Sahu SK, Kassis AI, Makrigiorgos GM, et al (1995). The effects ofIndium-111 decay on pBR322 DNA.
Radiat. Res. 141
Humm JL, Howell RW and Rao DV (1994). Dosimetry of Auger-electron-emitting radionuclides: Report No. 3 ofAAPM nuclear medicine task group No. 6
Med. Phys. 21
Howell RW, Kassis AI, Adelstein SJ, et al (1994). Radiotoxicity of platinum-195m-labeled trans-platinum(II) in mammalian cells.
Radiat. Res. 140
Macklis RM, Kinsey BM, Kassis AI, et al (1988). Radioimmunotherapy with alpha-particle-emitting immunoconjugates.
Zalutsky MR, Garg PK, Friedman HS and Bigner DD (1989). Labeling monoclonal antibodies and F(ab’)
fragments with the a-particle-emitting nuclide astatine-211: Preservation of immunoreactivity and
in vivo localizing capacity
. Proc. Natl. Acad. Sci. USA 86
, 7149–7153.ADSCrossRefGoogle Scholar
Junghans RP, Dobbs D, Brechbiel MW, et at (1993). Pharmacokinetics and bioactivity of
,N’’’-tetraacetic acid (DOTA)-bismuth-conjugated anti-Tac antibody for
. Cancer Res. 53
, 5683–5689.Google Scholar
Feinendegen LE and McClure JJ (1996). Workshop: Alpha Emitters for medical therapy.
Häfeli UO, Sweeney SM, Beresford BS, et al (1994). Biodegradable magnetically directed Y-microspheres: Novel agents for targeted intracavitary radiotherapy.
J. Biomed. Mat. Res. 28
Wise DL, Fellmann TD
, Sanderson JE and Wentworth RL (1979). Lactic/glycolic acid polymers.
In Drug carriers in biology and medicine. Gregoriadis G (Ed), Academic Press, London, pp. 237–270.Google Scholar
Chu CC (1985). The degradation and biocompatibility of suture materials
. In CRC critical reviews in bio-compatibility. Williams DF (Ed), CRC Press, Boca Raton, Vol. 1, pp. 261–322.Google Scholar
Okada H and Toguchi H (1995). Biodegradable microspheres in drug delivery.
Crit. Rev. Ther. Drug Carr. Sys. 12
Eldridge JH, Staas JK, Chen D, et al (1993). New advances in vaccine delivery systems
. Seminars in Hematology 30
Suppl. 4, 16–25.Google Scholar
Tanguay JF, Zidar JP, Phillips HR and Stack RS (1994). Current status of biodegradable stems
. Cardiology Clinics 12
, 699–713.Google Scholar
Hnatowich DJ, Chinol M, Siebecker DA, et al (1988). Patient biodistribution of intraperitoneally administered Y-labeled antibody
J. Nucl. Med. 29
Wang S, Quadri SM, Tang XZ, et al (1995). Liver toxicity induced by combined external-beam irradiation and radioimmunoglobulin therapy.
Radiat. Res. 141
Herpst JM, Klein JL, Leichner PK, et al (1995). Survival of patients with resistant Hodgkin’s disease after polyclonal Yttrium-90 labeled antiferritin treatment.
J. Clin. Oncol. 13
Hopkins K, Chandler C, Bullimore J, et al (1995). A pilot study of the treatment of patients with recurrent malignant gliomas with intratumor Yttrium-90 radioimmunoconjugates.
Radiother. Oncol. 34
Humm JL and Cobb LM (1990). Nonuniformity of tumor dose in radioimmunotherapy.
J. Nucl. Med. 31
Berger MJ (1971). Distribution of absorbed dose around point sources of electrons and beta particles in water and other media.
J. Nucl. Med. 12
Suppl. 5, 5–23.ADSGoogle Scholar
Berger MJ (1973). Improved point kernels for electron and beta ray dosimetry.
NBSIR, 73–107.Google Scholar
Häfeli UO, Sweeney SM, Beresford BA, et al (1995). Effective targeting of magnetic radioactive Y-microspheres to tumor cells by an externally applied magnetic field. Preliminary
in vitro and in vivo results
. Nucl. Med. Biol. 22
, 147–155.CrossRefGoogle Scholar
Tomayko MM and Reynolds CP (1989). Determination of subcutaneous tumor size in athymic (nude) mice.
Cancer Chemother. Pharmacol. 24
Kooistra KL, Rodriguez M, Powis G, et al (1986). Development of experimental models for meningeal neoplasia using intrathecal injection of 9L gliosarcoma and walker 256 carcinosarcoma in the rat
. Cancer Res. 46
, 317–323.CrossRefGoogle Scholar
Deutsch M (1988). Medulloblastoma: Staging and treatment outcome.
Int. J. Radial. Oncol. Biol. Phys. 14
Friedman HS, Oakes WJ, Bigner SH, et al (1991). Medulloblastoma tumor: Biological and clinical perspectives.
J. Neuro-Oncol. 11
Howard MA, Grady MS, Ritter RC, et al (1989). Magnetic movement of a brain thermoceptor
. Neurosurgery 24
, 444–448.CrossRefGoogle Scholar
Grady MS, Howard MA, Broaddus WC, et al (1990). Magnetic stereotaxis: A technique to deliver stereo-tactic hyperthermia.
Stabin MG (1996). MIRDOSE: Personal computer software for internal dose assessment in nuclear medicine.
J. Nucl. Med. 37
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