TCRT June 2004

category image Volume 3
No. 3 (p 229-308)
June 2004
ISSN 1533-0338
Photodynamic Therapy

Improved Targeting of Photosensitizers by Intratumoral Administration of Immunoconjugates (p. 295-302)

Biodistribution of technetium (99mTc) labeled hematoporphyrin derivative (HpD, Photosan-3) conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) was compared following intravenous (i.v.) and intratumoral (i.t.) administration in solid Ehrlich ascites tumor bearing mice. Images of mice at different time intervals were acquired after injection of radiolabeled PS-3 in either conjugated or unconjugated forms. Quantitative estimation of the radiolabel in different tissues was performed by selecting the different region of interests (ROIs). Maximum accumulation of both free and antibody conjugated PS-3 following i.v. administration was observed in liver followed by tumor. Tumor/muscle (T/N) ratio was more with free PS-3 compared to conjugated PS-3. Pharmacokinetics of free and conjugated PS-3 was also different with faster accumulation of conjugated PS-3 in the tumor. With intratumoral administration of anti-CEA-PS-3-99mTc, specific accumulation and retention of the sensitizer was observed in the tumor tissue. Since, direct injection of antibody conjugated photosensitizer into the tumor resulted in longer retention of the dye in the tumor with no accumulation in the normal tissues, the present results imply that the toxicity to normal tissues could be reduced significantly with selective destruction of the tumor following photodynamic treatment with the use of i.t. administration of specific antibodies conjugated to photosensitizers.

Key words: Photosan-3, Monoclonal antibody, CEA, Intratumoral administration, Photosensitization, Biodistribution, Immunoconjugates, Ehrlich ascites tumor.

Seema Gupta, Ph.D.1a*
A.K. Mishra, Ph.D.1
K. Muralidhar, Ph.D.2
Viney Jain, Ph.D.3

1Division of Biocybernetics and Radiopharmaceuticals
Institute of Nuclear Medicine and Allied Sciences
Brig. S. K. Mazumdar Road
Timarpur, Delhi-110054, India
2Department of Zoology
University of Delhi
Delhi-110007, India
3Department of Emergency Medicine
and Department of Nuclear Medicine
Kettering Medical Center
Wright State University
Dayton, OH 45429, USA

aPresent Address:
Department of Radiation Medicine
University of Kentucky
Lexington, KY 40536, USA
*sgupt3@uky.edu

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