Bone uptake

Calcitonin (peptide) bones Uptake of Ca2+ from blood to bone ... 

Dikanov, S.A., B.D. Liboiron, and C. Orvig. 2002. Two-dimensional (2D) pulsed electron paramagnetic resonance study of V02+-triphosphate interactions Evidence for tridentate triphosphate coordination, and relevance to bone uptake and insulin enhancement by vanadium pharmaceuticals. J. Am. Chem. Soc. 124 2969-2978. 

Bone uptake may also influence plasma fluoride concentrations. Studies in rats have demonstrated that metabolic acidosis increases the rate of bone resorption... 

The proportion of a Tc bone agent which is taken up by bone after intravenous injection will be affected by its binding to proteins in the blood serum. The proportions of the plasma Tc which were protein bound two hours after administration were found to be 16, 31, 54 and 85% with HEDP, MDP, PYP and tripolyphosphate respectively. In addition, the proportion of the administered dose of Tc which was taken up in bone was found to increase linearly with the fraction of Tc in the plasma which was not protein bound. Cox has reported a linear decrease in bone uptake with molecular weight for this series of bone agents, an observation which appears to reflect differences in their plasma protein binding behaviour. Thus the blood serum proteins may compete with bone for the Tc complexes and reduce the bone labelling efficiency of the radiopharmaceutical. The "Tc-diphosphonate formulations showed better performance in this respect than "Tc-PYP or Tc-tripolyphosphate. 

Evaluation of tumour lesion to normal bone uptake ratio... 

The tumour lesion to normal bone uptake (T/N) ratio values obtained by Re-HEDP scans are given in Table 7.2. They were found to range between... 

TABLE 7.2. TUMOUR TO NORMAL BONE UPTAKE (T/N) RATIO FOR ""Rc-HEDP... 

In this study, dogs with spontaneous osteosarcomas were used as a pathological animal model to examine accumulation of Re-HEDP in bone tumour lesions. As reported, owing to in vivo oxidation of rhenium, Re-HEDP is washed out faster from normal bone than from abnormal bone tumour lesions. The resulting increase in the tumour to normal bone uptake ratio is a favourable feature for a therapeutic bone agent. For this reason, the tumour to normal bone uptake ratio in the image recorded was calculated approximately... 

A recent development is the use of radioactive metal-ethylenedia-minetetramethylenephosphonate (EDTMP) complexes (Figure 7.3) for the relief of pain from tumour deposits in bone. These complexes localize in bone, especially in areas infiltrated with tumour, and the pain relief results from the radiation dose delivered by the radioactive metal which has co-located at the sites with the EDTMP. Both Sm and Ho seem appropriate (t /2 = 46 and 27 h, and -particle emission 0.7 and 1.9 MeV, respectively). However, the Ho-EDTMP complex has a much poorer bone uptake than the corresponding Sm complex (18% versus respectively) and this is reflected in the pain alleviation... 

McCarthy ID, Hughes SPF. 1989. Multiple tracer studies of bone uptake of 99mTc-M.P. and 85Sr. Am J Physiol 256 H1261-H1265. 

Shimmins J, Smith DA. 1972. Discrimination between calcium and strontium in bone uptake and loss. In International Conference on Strontium Metabolism, ed. Second international conference on strontium metabolism, Glasgow and Strontian, 16-19 August, 1972. TID 4500 59th ed. Health and Safety Laboratory / U.S. Atomic Energy Commission, 389-396. 

Walinder G, Feinstein RE, Gimeno EJ. 1986. Effect of high 131I doses on the bone uptake and retention of 90Sr and 90Y. Acta Radiol Oncol 25 255-260. 

Bone uptake may also influence plasma fluoride... 

After intravenous infusion of iron containing drugs or in cases of chronic iron overload in chronic diseases, a change in the bone-to-kidney ratio of diphosphonate complexes has been reported, namely, a decrease in bone uptake and an increase in accumulation in renal parenchyma (McRae et al. 1976). Dissociation of the Tc-diphos-phonate complex and a conversion into the renaltropic gluconate was proved in the presence of ionic iron(II) and calcium. In vivo alteration of the complex was concluded from an increase in renal uptake even after infusion of dextrose. 

Long-term treatment with glucocorticosteroids results in a decrease in bone uptake. This phenomenon may not be explained as interference between a pharmaceutical and a radiopharmaceutical but by the drug-induced osteoporosis (Conklin et al. 1983). 

Following intravenous injection, 45-50% of " Tc-diphosphonates (MDP, HDP, DPD) accumulate in the skeleton, while most of the rest is excreted in the urine. Maximum bone accumulation occurs 1 h after injection and remains constant for 72 h. The determining factors for bone uptake of " Tc-phosphonate complexes are an increased blood flow to the skeleton and reactive bone formation, causing avid extraction by the bone mineral matrix (Jones et al. 1976 Sahni et al. 1993). Symmetric areas of increased activity concentration are seen in the metaphyseal zones in the growing skeleton. Ankles, knees, elbows, wrists, shoulder joints, pelvic bones, and vertebrae show increased uptake in the normal anterior bone scintigram (Saha 1987). 

Besides an increase in the osteogenic activity, bone uptake of " Tc-diphosphonates is closely related to chemical structure, as demonstrated by the skeletal uptake of... 

Tc radiolabelled diphosphonate is injected intravenously and is rapidly absorbed into the extracellular fluid. Although the exact mechanism of uptake of the radiopharmaceutical from the extracellular fluid into the bone is not completely understood, it is thought that both the osteoblastic activity and vascularity of the bone have roles. Following uptake the radiopharmaceutical is then adsorbed onto the surface of the inorganic crystalline bone matrix. A few hours post injection the blood level is approximately 3.5% of the injected dose and bone uptake is at 50% of the injected dose (Thrall and ZiESSMAN 2001 Haasbeek and Green 1994). 

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