History and current uses of 224Ra in ankylosing spondylitis and other diseases

doi:10.1016/0160-4120(93)90272-J

Environment International

Volume 19, Issue 5, 1993, Pages 467-473

https://doi.org/10.1016/0160-4120(93)90272-J Get rights and content

Abstract

During and briefly after World War II, ²²⁴Ra was used in a German hospital in combination with platinum and eosin (Peteosthor) for the treatment of tuberculosis and ankylosing spondylitis. The patients, primarily children and juveniles, received repeated intravenous injections of up to 2 MBq ²²⁴Ra per injection twice a week for months, sometimes even for years. Injected amounts totalled up to 140 MBq. Following this therapy, an enormous increase in the incidence of bone tumors (56 cases among 900 patients), as well as other lesions was observed. The surviving patients are still under follow-up. Treatment of ankylosing spondylitis with drastically reduced doses of ²²⁴Ra, however, was continued up to the recent present and over 1500 patients were so treated in West-German hospitals. This second cohort, exclusively adults, received much lower amounts applied in most cases as one series of 10 weekly injections of about 1 MBq of ²²⁴Ra each. This would result in a cumulative alpha-dose of about 0.56 Gy to the marrow-free skeleton of a 70 kg man. These patients have been followed for several years, together with a control group of ankylosing spondylitis patients not treated with radioactive drugs or x-rays. By August 1991, three cases of malignant bone tumors have been observed among the exposed (0.7 – 2.4 cases expected) vs. one case among the controls. Diseases of hematopoietic tissue included leukemias (9 in the exposure group vs. 6 in the control group) and bone marrow failure (12 cases vs. 9). The increase of total leukemias among the exposed, compared to a standard population, is highly significant (9 cases observed vs. 2.8 expected, p < 0.003). Chronic myeloid leukemia, specifically, was elevated in the exposed group (3 cases observed vs. 0.8 expected, p = 0.047) but not in the control group.

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The heaviest group 2 element radium delivers two isotopes of high relevance for targeted alpha therapy: 223Ra and 224Ra. For a number of decades in the past, 224Ra (t1/2 = 3.6 d) has been applied as SpondylAT® for the treatment of Morbus Bechterew [11,12], but lost its approval in 2006 due to regulatory issues. Moreover, a study with 1471 ankylosing spondylitis patients who have received SpondylAT® pointed out the risk to develop myeloproliferative diseases [13].
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History and current uses of 224Ra in ankylosing spondylitis and other diseases

Abstract

Int. J. Oral Surg.

Eur. J. Pediatr.

Use of radium-224 in the treatment of ankylosing spondylitis and rheumatoid synovitis

Health Phys.

Über die funktionelle Therapie bei der Spondylitis ancylopoetica in Verbindung mit Thorium X-Gaben

Arch. Orthop. Unfall-Chir.

Weitere Beiträge zur ThX-Therapie bei Anämie, Leukämie und rheumatischen Erkrankungen

Berliner Klin. Wochenschr.

Time and dose dependency of bone sarcomas in patients injected with radium-224

Radiat. Environ. Biophys.

An epidemiological assessment of lens opafications with impaired vision in patients injected with radium-224

Radiat. Res.

The reverse protraction factor in the induction of bone sarcomas in radium-224 patients

Radiat. Res.

Klinik und Therapie der Spondylarthritis ankylopoetica-Behandlungsergebnisse mit Thorium X und Corticoiden

Zur Behandlung des Morbus Bechterew mit Thorium X. Wien. Klin.

Wochenschr.

La Spondylarthrite ankylosante

Ein Beitrag zur Thorium-X-Therapie bei der Spondylitis ankylosans

Spätschäden am Odonton nach Behandlung mit Thorium X

Dtsch. J. Mund-Kiefer-Gesichts-Chir.

Nachuntersuchungen an mit Peteosthor bzw. Thorium X behandelten M. Bechterew-kranken des “Annastifts”

Thorium X in spondylitis and chronic rheumatism

Rheumatism

Strahlenkatarakt nach Peteosthorbehandlung (Thorium X)

Monatsbl. Augenheilk.

The induction by 224Ra of myeloid leukemia and osteosarcoma in male CBA mice

Inter. J. Radiat. Biol.

Über die Behandlung des Morbus Bechterew, insbesondere mit Thorium X

Dtsch. Gesundheitswes.

Erfolge und Gefahren bei der Behandlung des Morbus Bechterew mit Thorium X

Die Ergebenisse der intravenösen Thorium X-Behandlung bei der Spondylarthritis ankylopoetica (M. Bechtterew)

Strahlentherapie

Strahlenbedingte Wachstumsstuörungen der Gliedmassen

Indication for 224Ra-therapy in ankylosing spondylitis (Morbus Strumpell-Bechterew-Marie)

Zur Behandlung des Morbus Bechterew mit Thorium-X

Zur Frage von Spätschäden nach der Behandlung mit Thorium-X

Z. Orthop. Traumat.

Die Behandlung der Bechterew'schen Erkrankung mit Peteosthor

Med. Wochenschr.

Traitement des Rhumatismes Chroniques par le Thorium

Bulletins et mémoires de la Société Médicale des Hôpitaux de Paris

La thérapeutique médicamenteuse de la spondylarthrite ankylosante

Rev. Rhum.

Orales Thorium X als Mittel der Wahl beim Morbus Bechterew

Dtsch. Med. J.

Skeletal effects following 224Ra injections into humans

Health Phys.

Malignancies in patients injected with Radium-224

Ankylosing spondylitis

History and current uses of ²²⁴Ra in ankylosing spondylitis and other diseases

The induction by ²²⁴Ra of myeloid leukemia and osteosarcoma in male CBA mice

Indication for ²²⁴Ra-therapy in ankylosing spondylitis (Morbus Strumpell-Bechterew-Marie)

Skeletal effects following ²²⁴Ra injections into humans