thorium-x and Bone-Neoplasms

New treatments combating bone and extraskeletal metastases are needed for patients with metastatic castration-resistant prostate cancer. The majority of metastases overexpress prostate-specific membrane antigen (PSMA), making it an ideal candidate for targeted radionuclide therapy.. The aim of this study was to test a novel liquid 224Ra/212Pb-generator for the rapid preparation of a dual-alpha targeting solution. Here, PSMA-targeting ligands are labelled with 212Pb in the 224Ra-solution in transient equilibrium with daughter nuclides. Thus, natural bone-seeking 224Ra targeting sclerotic bone metastases and 212Pb-chelated PSMA ligands targeting PSMA-expressing tumour cells are obtained.. Two PSMA-targeting ligands, the p-SCN-Bn-TCMC-PSMA ligand (NG001), specifically developed for chelating 212Pb, and the most clinically used DOTA-based PSMA-617 were labelled with 212Pb. Radiolabelling and targeting potential were investigated in situ, in vitro (PSMA-positive C4-2 human prostate cancer cells) and in vivo (athymic mice bearing C4-2 xenografts).. NG001 was rapidly labelled with 212Pb (radiochemical purity >94% at concentrations of ≥15 μg/ml) using the liquid 224Ra/212Pb-generator. The high radiochemical purity and stability of [212Pb]Pb- NG001 were demonstrated over 48 hours in the presence of ascorbic acid and albumin. Similar binding abilities of the 212Pb-labelled ligands were observed in C4-2 cells. The PSMA ligands displayed comparable tumour uptake after 2 hours, but NG001 showed a 3.5-fold lower kidney uptake than PSMA- 617. Radium-224 was not chelated and, hence, showed high uptake in bones.. A fast method for the labelling of PSMA ligands with 212Pb in the 224Ra/212Pb-solution was developed. Thus, further in vivo studies with dual tumour targeting by alpha-particles are warranted.

Topics: Animals; Bone Neoplasms; Cell Line, Tumor; Disease Models, Animal; Humans; Lead Radioisotopes; Ligands; Male; Mice; Mice, Nude; Prostate-Specific Antigen; Prostatic Neoplasms; Radiopharmaceuticals; Radium; Thorium

For over five decades, osteochondromas (exostoses) and associated growth retardation have been known to be caused by radiation damage to the growing skeleton. Patients can be divided into three exposure groups. Group I received external beam radiation therapy primarily for the treatment of childhood cancers (typical dose 3,500 cGy), and 6-20% developed osteochondromas and growth retardation within the radiation portal. Group II consists of recently described patients who received total body irradiation in preparation for bone marrow transplant (typical dose: 800-1,200 cGy), and about 20% developed osteochondromas and growth retardation. Group III consists of 206 German children who in the 1940s and early 1950s received intravenous radioactive Peteosthor (Ra-224) to treat bone tuberculosis (estimated typical dose: 1,000-2,000 cGy), and 14% developed osteochondromas and growth retardation, among other benign and malignant sequelae. Combining these three exposure groups, osteochondromas and growth retardation develop in at least 6-20% of children who receive therapeutic radiation to their growing skeletons.

Topics: Bone and Bones; Bone Development; Bone Marrow Transplantation; Bone Neoplasms; Child; Growth Disorders; Humans; Infant; Neoplasms; Osteochondroma; Radiation Dosage; Radiopharmaceuticals; Radiotherapy; Radium; Thorium; Transplantation Conditioning; Tuberculosis, Osteoarticular; Whole-Body Irradiation

This paper analyzes data for the osteosarcoma incidence in life-time experiments of (224)Ra injected mice with respect to the importance of initiating and promoting action of ionizing high LET-radiation. This was done with the biologically motivated two step clonal expansion (TSCE) model of tumor induction. Experimentally derived osteosarcoma incidence in 1,194 mice following exposure to (224)Ra with different total radiation doses and different fractionation patterns were analyzed together with incidence data from 1,710 unirradiated control animals. Effects of radiation on the initiating event and on the clonal expansion rate, i.e. on promotion were found to be necessary to explain the observed patterns with this model. The data show a distinct inverse protraction effect at high doses, whereas at lower doses this effect becomes insignificant. Such a behavior is well reproduced in the proposed model: At dose rates above 6 mGy/day a longer exposure produces higher ERR per dose, while for lower rates the reverse is the case. The TSCE model permits the deduction of several kinetic parameters of a postulated two-step bone tumorigenesis process. Mean exposure rates of 0.13 mGy/day are found to double the baseline initiation rate. At rates above 100 mGy/day, the initiation rate decreases. The clonal expansion rate is doubled at 8 mGy/day, and it levels out at rates beyond 100 mGy/day.

Topics: Animals; Bone Neoplasms; Female; Mice; Models, Biological; Neoplasms, Radiation-Induced; Osteosarcoma; Radium; Risk Assessment; Thorium

Mainly between 1945 and 1955, several thousand German patients with ankylosing spondylitis, tuberculosis, or--in a few cases--other diseases received multiple injections of the short-lived alpha-particle emitter radium-224. In the early 1950s, the follow-up of 899 patients was initiated, and the study has continued since then. It includes most of the high-dose patients and nearly all of those treated as children or juveniles, i.e. under the age of 21. In the study cohort, 56 malignant bone tumors occurred in a temporal wave that peaked 8 years after exposure, whereas less than one case would have been expected during the follow-up. Most of the malignant bone tumors were osteosarcomas and fibrous-histiocytic sarcomas. A new analysis has now been performed, primarily because an improved dosimetry resulted in modified bone surface doses, especially for those treated at younger ages. A significant increase in bone tumor risk with decreasing age at exposure is now demonstrated. The earlier finding of an inverse protraction factor is confirmed. In the new formulation, the dependence on dose rate or duration applies only at higher doses; i.e., the initial slope of the dose dependence is unrelated to dose rate or exposure duration, which is in contrast to earlier analyses but is in agreement with microdosimetric considerations and general radiobiological experience.

Topics: Adolescent; Adult; Age Distribution; Age Factors; Bone Neoplasms; Child; Chordoma; Cohort Studies; Dose-Response Relationship, Radiation; Female; Follow-Up Studies; Germany; Humans; Incidence; Likelihood Functions; Lymphoma; Male; Neoplasms, Radiation-Induced; Radiometry; Radium; Risk Assessment; Sarcoma; Sex Distribution; Thorium

Topics: Bone Neoplasms; Humans; Neoplasms, Radiation-Induced; Radium; Sarcoma; Thorium

Topics: Adolescent; Adult; Aged; Bone Neoplasms; Child; Female; Follow-Up Studies; Germany, West; Humans; Male; Neoplasms, Radiation-Induced; Radium; Sarcoma; Spondylitis, Ankylosing; Thorium; Time Factors; Tuberculosis

Topics: Adolescent; Adult; Bone Neoplasms; Child; Female; Follow-Up Studies; Germany, West; Humans; Male; Neoplasms, Radiation-Induced; Radiation Dosage; Radium; Sarcoma; Thorium

Topics: Bone Neoplasms; Female; Follow-Up Studies; Germany, West; Humans; Leukemia, Radiation-Induced; Male; Neoplasms, Radiation-Induced; Radiation Dosage; Radium; Risk; Spondylitis, Ankylosing; Thorium; Time Factors

Topics: Animals; Bone Neoplasms; Dose-Response Relationship, Radiation; Female; Lutetium; Mice; Neoplasms, Radiation-Induced; Radioisotopes; Radium; Sarcoma, Experimental; Thorium

Topics: Bone and Bones; Bone Neoplasms; Humans; Neoplasms; Neoplasms, Radiation-Induced; Osteosarcoma; Radiation Injuries; Radium; Sarcoma; Thorium