Labeling conditions, in vitro properties and biodistributions of various Sn-labeled complexes.

Conditions for preparing Sn-EDTMP, Sn-DTPMP, Sn-TTHMP, Sn-HEDTMP and Sn-DTPA in aqueous solution in open air environments, and their in vitro properties including adsorption on hydroxyapatite (HA) and collagen (I) and binding to bovine serum albumin (BSA) were studied using (117m)Sn and 113Sn as tracers. Biodistributions of SnO2.xH2O.yEDTMP, SnO2.xH2O.yDTPMP, SnO2.xH2O.yTTHMP, SnO2.xH2O.yHEDTMP, SnO2.xH2O.yDTPA in normal mice were also tested. Based on the above experiments, the relationship between in vitro biochemical properties and biodistributions of these SnO2.xH2O.yLigands was investigated. The results show that Sn(IV)-Ligands are prone to hydrolysis into SnO2.xH2O.yLigands in aqueous solutions in open air environments, especially when the ligand is DTPA, when the molar ratio of metal to ligand is higher than 1:200, or when the pH of the solution is higher than 10. The in vitro experiments show that all of the SnO2.xH2O.yLigands bind strongly to BSA, and the binding percentages of SnO2.xH2O.yLigands to BSA are much higher than those of the corresponding Sn(IV)-Ligands. The biodistribution data indicate that all of the SnO2.xH2O.yLigands locate mainly in bone with little uptake in liver. When the binding percentages of SnO2.xH2O.yLigands to BSA are similar, those SnO2.xH2O.yLigands with higher adsorption on HA and collagen (I) undergo lower liver uptake.

Biodistribution and pharmacokinetics of variously molecular sized 117mSn(II)-polyethyleneiminomethyl phosphonate complexes in the normal primate model as potential selective therapeutic bone agents.

In the search for a cure for metastatic bone cancer, 117mSn with its conversion electrons and low energy photons both of discrete energies shows little bone marrow toxicity, providing the opportunity to increase the administered dose. Selective accumulation in lesions would capitalise on this advantage. The 10-30 kDa fraction of the water-soluble polymer polyethyleneimine, functionalised with methyl phosphonate groups (PEI-MP) and labelled with 99mTc, has shown selective uptake into bone tumours. Furthermore using speciation calculations it was predicted that the Sn(II)-PEI-MP complex would remain intact in the blood plasma. Because of this positive indication animal experiments were carried out to test this prediction. This paper relates the labelling, biodistribution and pharmacokinetics of various fractions of 117mSn-(II) PEI-MP in the normal primate model, and points to promising therapeutic possibilities.

In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice.

Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a gamma-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. Gamma-ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogeneous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected dose at 24 h and the rest was excreted. At 24 h postinjection, bone in mice showed 84.2% of the whole-body retention, muscle 1.7% and liver 1.4%, and the rest was distributed in other soft tissues. Percent distribution of the retained dose among bone, muscle, liver and other soft tissues is very similar between mice and a human subject. To calculate precise radiation absorbed doses from bone pain palliation radionuclides, it is necessary to take into account soft-tissue uptake and retention that may not be readily evident from routine external gamma-scintigraphy.

Cancer therapy using bone-seeking isotopes.

Bone pain is a common symptom in disseminated malignancy and may be difficult to manage effectively. Radiation is of proven benefit for pain palliation and there is growing interest in the therapeutic potential of bone-seeking radiopharmaceuticals. Clinical data relating to the use of phosphorus-32, strontium-89, samarium-153 EDTMP, rhenium-186 HEDP and tin-117m DTPA are reviewed in the context of the pathophysiology of metastatic bone pain. Possible mechanisms of action of palliative radiotherapy and, in particular, the theoretical role of early response genes are discussed. The application of Monte Carlo simulation to targeted radiotherapy for bone metastases may provide the basis for a clearer understanding of the microdosimetry and radiobiology of bone pain palliation and for reliable prediction of clinical response and toxicity.