Clinical Evaluation of Radio-Labelled Bleomycin for Tumor Detection

J. J. Rasker; H. Beekhuis; M.A.P.C. van de Poll; A. Versluis; H. Jurjens; M.G. Woldring

doi:10.1055/s-0037-1620700

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 1978; 17(06): 238-248
DOI: 10.1055/s-0037-1620700

Originalarbeiten – Original Articles

Schattauer GmbH

Clinical Evaluation of Radio-Labelled Bleomycin for Tumor Detection

Klinische Erfahrungen mit markierten Bleomycinen für den Tumornachweis

J. J. Rasker

¹From the Isotopic Laboratory, Rijksuniversity, Groningen, The Netherlands

,

H. Beekhuis

¹From the Isotopic Laboratory, Rijksuniversity, Groningen, The Netherlands

,

M.A.P.C. van de Poll

¹From the Isotopic Laboratory, Rijksuniversity, Groningen, The Netherlands

,

A. Versluis

¹From the Isotopic Laboratory, Rijksuniversity, Groningen, The Netherlands

,

H. Jurjens

¹From the Isotopic Laboratory, Rijksuniversity, Groningen, The Netherlands

,

M.G. Woldring

¹From the Isotopic Laboratory, Rijksuniversity, Groningen, The Netherlands

› Author Affiliations

Abstract

Investigations with bleomycin labelled with radionuclides other than ⁵⁷Co in patients with cancer and in tumor-bearing animals are described. In patients ⁵⁷Co-bleo appears to be a better tumor-seeking radiopharmaceutical than ¹¹¹In-bleo, ^99mTc-bleo or ¹⁹⁷Hg-bleo. This can be explained by a higher stability in vivo and a better tumor-seeking property of ⁵⁷Co-bleo and less disturbing activity in the cardiac pool and in bone and other normal tissues when assessing the scintigram.

Results with ¹¹¹In-bleo labelled in acidic solution are not essentially different from those with ¹¹¹In-bleo labelled in neutral solution.

Results of ¹⁹⁷Hg-bleo are almost identical with those of ¹⁹⁷HgCl₂ regarding the tumor-seeking effect as well as the distribution in normal tissues and organs. Probably the complex of ¹⁹⁷Hg to bleomycin is not stable in vivo. The superiority of ⁵⁷Co-bleo over ^99mTc-bleo, ¹⁹⁷Hg-bleo and also over ⁶⁷Cu-bleo is confirmed by experiments on tumor bearing animals.

We may conclude that the indication for use of bleomycin as a tumor-seeking pharmaceutical labelled with ¹¹¹In, ^99mTc, ¹⁹⁷Hg or ⁶⁷Cu seems to be very limited.

Es werden klinische und tierexperimentelle Verteilungsstudien mit ⁵⁷Co-, ¹¹¹In-, ^99mTc-, ¹⁹⁷Hg- und ⁶⁷Cu-Bleomycin beschrieben.

Bei Patienten zeigte sich, daß ⁵⁷Co-Bleo als Radiopharmakon in der Tumorszintigraphie den Präparaten ¹¹¹In-Bleo, ^99mTc-Bleo oder ¹⁹⁷Hg-Bleo überlegen ist. Die Ursache ist eine größere Stabilität in vivo und bessere Eigenschaften des ⁵⁷Co-Bleo zum Nachweis von Tumoren und eine in der Beurteilung des Szintigramms weniger störende Radioaktivität im Herzpool und in den Knochen und anderen normalen Geweben.

Die Resultate mit in sauren Lösungen markiertem ¹¹¹In-Bleo sind von denen mit in neutralen Lösungen markiertem ¹¹¹In-Bleo nicht wesentlich verschieden.

Die Ergebnisse mit ¹⁹⁷Hg-Bleo sind fast identisch mit denen mit ¹⁹⁷Hg Cl₂ sowohl im „Tumor-Nachweis-Effekt” als auch in der Verteilung in normalen Geweben und Organen. Wahrscheinlich ist in vivo der Komplex von ¹⁹⁷Hg mit Bleomycin nicht stabil.

⁵⁷Co-Bleo ist ^99mTc-Bleo, ¹⁹⁷Hg-Bleo und auch ⁶⁷Cu-Bleo überlegen, wie durch Experimente bei Tieren mit Tumoren bestätigt wird.

Dies führt zum Schluß, daß die Indikation zur Verwendung von Bleomycin als mit ¹¹¹In, ^99mTc oder ¹⁹⁷Hg markiertes Pharmakon zum Nachweis von Tumoren begrenzt ist.

Full Text

References

References
1 Anghileri L. J. Studies on the accumulation mechanism of radioisotopes used in tumor diagnostic. Strahlentherapie 1971; 142: 456.
2 Barendsen G. W, Roelse H, Hermens A. F. et al. Clonogenic capacity of proliferating and non-proliferating cells of a transplantable rat rhabdomyosarcoma in relation to its radiosensi-tivity. J. natl. Cancer Inst 1973; 51: 1521.
3 Brown L. C, Callahan A. P. The separation and purification of carrier-free copper isotopes for medical use. Int. J. appl. Radiat 1972; 23: 535.
4 Coates G, Aspin N, Wong P. Y. et al. ⁶⁷Cu as a label for bleomycin. (Abstr.) J. nucl. Med 1974; 15: 484.
5 Eckelman W. C, Reba R. C, Kubota H. et al. Early detection of mammary carcinoma with radiolabelled bleomycin, (Abstr. J. nucl. Med 1974; 15: 489.
6 Farrer P. A, Saba G. B, Munro D. D. et al. Radionuclide imaging of intrathoracic mass lesions using ¹⁹⁷HgCl₂ and ^99mTc-macroaggregated human serum albumin. (Abstr.) J. nucl. Med 1974; 15: 490.
7 Goodwin D. A, Lin M. S, Diamanti C. I. et al. ¹¹¹In-labelled bleomycin for tumor localization by scintiscanning. (Abstr.) J. nucl. Med 1973; 14: 401.
8 Graham L. S, Verma R. C, Touya J. J. et al. Relative tissue concentration and radiation dosimetry of ¹¹¹In-bleomycin. Int. Symp. on Radiopharmaceuticals, Atlanta, USA, February 1974
9 Grove R. B, Eckelman W. C, Reba R. C. Distribution of labelled bleomycin in normal and tumor-bearing mice. J. nucl. Med 1973; 14: 917.
10 Grove R. B, Reba R. C, Eckelman W. C. et al. Clinical evaluation of radiolabelled bleomycin (bleo) for tumor detection. J. nucl. Med 1974; 15: 380.
11 Hall J. N, O’Mara R. E. ⁶⁷Cu-Bleomycin: a tumor localizing agent. (Abstr.). J. nucl. Med 1974; 15: 498.
12 Hayes R. L, Edwards C.L. New applications of tumor-localizing radiopharmaceuticals. Symposium on Medical Radioisotope Scintigraphy. Monte Carlo (IAEA), 1972
13 Hermens A. F, Barendsen G. W. Cellular proliferation patterns in an experimental rhabdamyosarcoma in the rat. Eur. J. Cancer 1967; 3: 361.
14 Hoffer P. B, Gottschalk A. Tumor scanning agents. Sem. Nucl. Med 1974; 4: 305.
15 Horn N. L, Verma R. C, Bennett L. R. Systemic in-depth analysis of normal indium-111 bleomycin scans. (Abstr.) J. nucl. Med 1975; 16: 536.
16 de Jong P. C. The use of ¹⁹⁷HgCl₂ in diagnosis of malignant tumours of the head and neck region. O R L 1972; 34: 303.
17 Kono A, Kojima M, Maeda T. The tumor specific localizing agents for radioisotope image. The preparation of labelled bleomycins and their distributions in the tumor bearing mice. Radioisotopes 1972; 21: 64.
18 Lilien D. L, Jones S. E, O’Mara R. E. et al. A clinical evaluation of indium-bleomycin as a tumor imaging agent. Cancer 1975; 35: 1036.
19 Lin M. S, Goodwin D. A, Kruse S. L. Bleomycin as a ^99mTc carrier in tumor visualization. J. nucl. Med 1974; 15: 338.
20 Medi + PhysicsIndium- 111 -bleomycin for scintigraphic diagnosis of tumors. 1974
21 Merrick M. V, Gunasekera S. W, Lavender J. P. et al. The use of indium 111 for tumour localization. A comparison of several chelates with gallium 67 in inflammatory and neoplastic lesions, with a note on indium-labeled bleomycin. Medical Radioisotope Scintigraphy IAEA (Vienna) 1972; 2: 721.
22 Merrick M. V, Lavender J. P, Poole G. W. et al. ¹¹¹In-labelled bleomycin, clinical experience as a diagnostic agent in tumours of the thorax and abdomen. Brit. J. Radiol 1975; 48: 279.
23 Monod O, Rymer M. Chemotherapeutic drugs marked with radioactive isotopes. Cancer Chemother. Rep. Part 3, 1973; 4: 245-249.
24 Mori T, Odori T, Sakamoto T. et al. Clinical results of ^99mTc-labelled bleomycin scintigraphy for tumor imaging Proc. Tokyo: First World Congress Nucl. Med.; 1974: 703
25 Mori T, Hamamato K, Onoyama J. et al. Tumor imaging after administration of ^99mTc-labelled bleomycin. J. nucl. Med 1975; 16: 414.
26 Nouel J. P, Robert J, Witz H. et al. Le diagnostic des tumeurs malignes et de leur extension par la bléomycine marquée au ⁵⁷Co. Radioaktive Isotope in Klinik und Forschung, 10. Band. Gasteiner Internationales Symposium 1972: S. 503
27 O’Mara R. E, Heber K, Corriga J. Indium- 111-bleomycin as a tumor scanning agent in pediatric oncology. (Abstr.) J. nucl. Med 1975; 16: 554.
28 Orii H, Oyamada H. Rl-labelled bleomycin - a critical investigation on their stability in vitro and in vivo. Tokyo: Proc. First World Congress Nucl. Med; 1974: 931
29 Oyamada H, Ishibashi H, Orii H. Clinical experiences of tumor seeking agents after Ga-67 citrate and the comparison between them. Tokyo: Proc. First World Congress Nucl. Med; 1974: 707
30 van de Poll M. A. P. C, Versluis A, Rasker J. J. et al. Labelling of bleomycin with cobalt-57, indium-111, technetium-99m, mercury-197, lead-203 and copper-67. Nucl.-Med 1976; XV: 86.
31 van Putten L. M. Tumour reoxygenation during fractionated radiotherapy; studies with a transplantable mouse osteosarcoma. Eur. J. Cancer 1968; 4: 173.
32 Rasker J. J. Het opsporen van tumoren met radioactief gemerkt bleomycine. Thesis Groningen. Drukkerij van Dende-ren B. V. 1975
33 Rasker J. J, Beekhuis H, van der Wal A. M. et al. Cobalt-57 bleomycin scanning of hila and mediastinum in patients with bronchial carcinoma: a prospective study. Thorax 1976; 31: 641.
34 Rasker J. J, van de Poll M. A. P. C, Beekhuis H. et al. Some experiences with cobalt- 57 labelled bleomycin as tumor localizing agent. J. nucl. Med 1976; 16: 1058.
35 Reba R. C, Eckelman W. C, Poulouse K. P. et al. Tumor specific radiopharmaceuticals: radiolabelled bleomycin. Int. Symp. on Radiopharmaceuticals, Atlanta USA: 1974. February
36 Renault H, Rapin J, Rudler M. et al. La chélation de divers cations radioactifs par certains polypeptides utilisée comme méthode de marquage. Application à la bléomycin. Bull. Chim. Therp 1972; 3: 232.
37 Robbins P. J, Silberstein E. B, Fortman D. L. ¹¹¹In-bleomy-cin kinetics in mice bearing transplantable tumors of lung, skin and bone. J. nucl. Med 1974; 15: 273.
38 Taylor D. M. Radiopharmaceuticals for tumour localisation-Rapporteur report. In: Radioactive Materials in the Investigation of Tumours. McCready V. R. et al. eds W. Heinemann Med. Books Ltd.: 1969
39 Taylor D. M. Comparison of ⁵⁷Co, ⁶²Zn and ¹¹¹In bleomycin complexes for tumor localization. Int. Symp. on Radiopharmaceuticals, Atlanta, USA, February 1974
40 Thakur M. L, Merrick M. V, Gunasekera S. W. Some phar-maceuticological aspects of a new radiopharmaceutical, ¹¹¹In-bleomycin. Radiopharmaceuticals and Labelled Compounds, Vol. II IAEA, Vienna: 1973: 183
41 Thakur M. L. The preparation of Indium 111-labelled bleomycin for tumour localisation. Int. J. appl. Radiat 24: 357-359. 1973;
42 Tragi K. H, Pils P, Angelberger P. et al. Bleomycin als Trägersubstanz für “Technetium in der Tumordiagnostik. Wien. klin. Wschr 1975; 87: 308.
43 Verma R. C, Touya J. J, Bennet L. R. Further observations on indium-111 labelled bleomycin for scanning tumors in man, (Abstrct). J. nucl. Med 1974; 15: 541.
44 Verma R. C, Silverstein M. J, Greenfield L. D. et al. Role of Indium- 111 bleomycin in predicting malignancies of palpable breast masses(Abstr.). J. nucl. Med 1975; 16: 578.
45 Verma R. C, Silverstein M. J, Greenfield L. D. et al. Correlation of indium-111 bleomycin breast scanning with other non-invasive techniques(Abstr.). J. nucl. Med 1975; 16: 578.
46 Wolf R. Lymph node scanning- Rapporteur report. In: Radioactive Materials in the Investigation of Tumours McCready V. R. et al. eds W. Heinemann Med. Books Ltd.: 1969