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. 1990 Jul;10:89–91.

Preparation and in vivo study of 124I-labelled monoclonal antibody H17E2 in a human tumour xenograft model. A prelude to positron emission tomography (PET).

D E Snook 1, G Rowlinson-Busza 1, H L Sharma 1, A A Epenetos 1
PMCID: PMC2149504  PMID: 2383487

Abstract

Positron emission tomography (PET) is a powerful nuclear medicine technique which, unlike conventional gamma camera tomography, relies on the coincidental detection of the two 511 keV gamma photons produced from the annihilation of a single positron. Hence good spatial resolution and accurate quantitation may be achieved. 124I (t1/2 = 4 days), a positron-emitting isotope of iodine, was chosen for our initial PET studies because the techniques of antibody radio-iodination are well established. The murine monoclonal antibody H17E2 detecting placental alkaline phosphatase (PLAP) was radiolabelled using the Iodogen method. A specific activity of 2.3 microCi microgram-1 was achieved with a radiolabelling efficiency of 91%. Nude mice bearing subcutaneous HEp2 human tumour xenografts (a PLAP expressing cell-line) received 8.3 micrograms (18.8 microCi) of H17E2-124I by intraperitoneal injection. Animals were killed and dissected at 5 h, 1, 2, 3, and 7 days, and radioactivity was assessed in tumour and normal tissues. The half-life in the blood of H17E2-124I was 132 h as compared with 141 h for H17E2-131I. Activity in tumour rose to 4.26% injected dose g-1 by 48 h and remained at this level until day 7, giving a tumour:blood ratio of 0.78 at this time. The percentage injected dose g-1 in all tissues (with the exception of tumour) decreased with time giving tumour:tissue ratios greater than 1.00 from 24 h onwards in all cases except blood. In conclusion, tumour localization of H17E2-124I has been successfully achieved in this animal model. This demonstrates the feasibility of using tumour-associated monoclonal antibodies radiolabelled with a positron-emitting isotope for tumour localization studies.

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Selected References

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  1. Beaney R. P., Lammertsma A. A., Jones T., McKenzie C. G., Halnan K. E. Positron emission tomography for in-vivo measurement of regional blood flow, oxygen utilisation, and blood volume in patients with breast carcinoma. Lancet. 1984 Jan 21;1(8369):131–134. doi: 10.1016/s0140-6736(84)90063-1. [DOI] [PubMed] [Google Scholar]
  2. Beaney R. P. Positron emission tomography in the study of human tumors. Semin Nucl Med. 1984 Oct;14(4):324–341. doi: 10.1016/s0001-2998(84)80006-9. [DOI] [PubMed] [Google Scholar]
  3. Epenetos A. A., Britton K. E., Mather S., Shepherd J., Granowska M., Taylor-Papadimitriou J., Nimmon C. C., Durbin H., Hawkins L. R., Malpas J. S. Targeting of iodine-123-labelled tumour-associated monoclonal antibodies to ovarian, breast, and gastrointestinal tumours. Lancet. 1982 Nov 6;2(8306):999–1005. doi: 10.1016/s0140-6736(82)90046-0. [DOI] [PubMed] [Google Scholar]
  4. Epenetos A. A., Snook D., Hooker G., Begent R., Durbin H., Oliver R. T., Bodmer W. F., Lavender J. P. Indium-111 labelled monoclonal antibody to placental alkaline phosphatase in in the detection of neoplasms of testis, ovary, and cervix. Lancet. 1985 Aug 17;2(8451):350–353. doi: 10.1016/s0140-6736(85)92495-x. [DOI] [PubMed] [Google Scholar]
  5. Frackowiak R. S., Lenzi G. L., Jones T., Heather J. D. Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography: theory, procedure, and normal values. J Comput Assist Tomogr. 1980 Dec;4(6):727–736. doi: 10.1097/00004728-198012000-00001. [DOI] [PubMed] [Google Scholar]
  6. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  7. Frey P., Townsend D., Jeavons A., Donath A. In vivo imaging of the human thyroid with a positron camera using 124I. Eur J Nucl Med. 1985;10(9-10):472–476. doi: 10.1007/BF00256597. [DOI] [PubMed] [Google Scholar]
  8. Hnatowich D. J., Snook D., Rowlinson G., Stewart S., Epenetos A. A. Preparation and use of DTPA-coupled antitumor antibodies radiolabeled with yttrium-90. Targeted Diagn Ther. 1988;1:353–374. [PubMed] [Google Scholar]
  9. Jones T., Chesler D. A., Ter-Pogossian M. M. The continuous inhalation of oxygen-15 for assessing regional oxygen extraction in the brain of man. Br J Radiol. 1976 Apr;49(580):339–343. doi: 10.1259/0007-1285-49-580-339. [DOI] [PubMed] [Google Scholar]
  10. Kalofonos H. P., Pawlikowska T. R., Hemingway A., Courtenay-Luck N., Dhokia B., Snook D., Sivolapenko G. B., Hooker G. R., McKenzie C. G., Lavender P. J. Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. J Nucl Med. 1989 Oct;30(10):1636–1645. [PubMed] [Google Scholar]
  11. Lambrecht R. M., Woodhouse N., Phillips R., Wolczak D., Qureshi A., Reyes E. D., Graser C., Al-Yanbawi S., Al-Rabiah A., Meyer W. Investigational study of iodine-124 with a positron camera. Am J Physiol Imaging. 1988;3(4):197–200. [PubMed] [Google Scholar]
  12. Lammertsma A. A., Wise R. J., Cox T. C., Thomas D. G., Jones T. Measurement of blood flow, oxygen utilisation, oxygen extraction ratio, and fractional blood volume in human brain tumours and surrounding oedematous tissue. Br J Radiol. 1985 Aug;58(692):725–734. doi: 10.1259/0007-1285-58-692-725. [DOI] [PubMed] [Google Scholar]
  13. Larson S. M., Brown J. P., Wright P. W., Carrasquillo J. A., Hellström I., Hellström K. E. Imaging of melanoma with L-131-labeled monoclonal antibodies. J Nucl Med. 1983 Feb;24(2):123–129. [PubMed] [Google Scholar]
  14. Moldofsky P. J., Powe J., Mulhern C. B., Jr, Hammond N., Sears H. F., Gatenby R. A., Steplewski Z., Koprowski H. Metastatic colon carcinoma detected with radiolabeled F(ab')2 monoclonal antibody fragments. Radiology. 1983 Nov;149(2):549–555. doi: 10.1148/radiology.149.2.6622704. [DOI] [PubMed] [Google Scholar]
  15. Rhodes C. G., Wise R. J., Gibbs J. M., Frackowiak R. S., Hatazawa J., Palmer A. J., Thomas D. G., Jones T. In vivo disturbance of the oxidative metabolism of glucose in human cerebral gliomas. Ann Neurol. 1983 Dec;14(6):614–626. doi: 10.1002/ana.410140604. [DOI] [PubMed] [Google Scholar]
  16. Stewart J. S., Hird V., Sullivan M., Snook D., Epenetos A. A. Intraperitoneal radioimmunotherapy for ovarian cancer. Br J Obstet Gynaecol. 1989 May;96(5):529–536. doi: 10.1111/j.1471-0528.1989.tb03251.x. [DOI] [PubMed] [Google Scholar]
  17. TOOLAN H. W. Transplantable human neoplasms maintained in cortisone-treated laboratory animals: H.S. No. 1; H.Ep. No. 1; H.Ep. No. 2; H.Ep. No. 3; and H.Emb.Rh. No. 1. Cancer Res. 1954 Oct;14(9):660–666. [PubMed] [Google Scholar]
  18. Ter-Pogossian M. M., Eichling J. O., Davis D. O., Welch M. J. The measure in vivo of regional cerebral oxygen utilization by means of oxyhemoglobin labeled with radioactive oxygen-15. J Clin Invest. 1970 Feb;49(2):381–391. doi: 10.1172/JCI106247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Travers P., Bodmer W. Preparation and characterization of monoclonal antibodies against placental alkaline phosphatase and other human trophoblast-associated determinants. Int J Cancer. 1984 May 15;33(5):633–641. doi: 10.1002/ijc.2910330514. [DOI] [PubMed] [Google Scholar]
  20. WEST J. B., DOLLERY C. T. Uptake of oxygen-15-labeled CO2 compared with carbon-11-labeled CO2 in the lung. J Appl Physiol. 1962 Jan;17:9–13. doi: 10.1152/jappl.1962.17.1.9. [DOI] [PubMed] [Google Scholar]

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