Does cisplatin chemotherapy decrease the MDP uptake of normal bone? An experimental study.

OBJECTIVE: Bone scan is the accepted initial imaging modality for skeletal metastases. Cisplatin is a cell-cycle nonspecific antineoplastic agent used in some chemotherapy regimens. Knowing that platinum reacts with phosphate compounds such as methylenediphosphonic acid (MDP), decreases bone resorption and new bone formation, it can be proposed that cisplatin chemotherapy may decrease Tc-99m MDP bone uptake. We aimed to demonstrate, if present, the decrease in bone uptake and to determine the duration of this effect. METHODS: Thirty male Wistar rats were randomized into five groups, namely, placebo group (G1) and cisplatin groups (G2, G3, G4, G5). Pre-therapy bone scintigraphies were obtained in all the groups. Cisplatin chemotherapy was given as infusion. Post-therapy bone scintigraphies were obtained 10 min, 1 h, 24 h, and 72 h after chemotherapy in groups G2-G5, respectively. A placebo bone scintigraphy was obtained 10 min after infusion of serum physiologic in G1. Plasma samples for cisplatin plasma values were obtained. The graphite furnace atomic absorption spectrophotometry technique was used for cisplatin analysis. Quantitative analysis (bone uptake ratios) was performed by drawing regions of interest on the right femur, vertebral column, and adjacent soft tissues. The injection/examination time delay and the net injected MDP doses were also noted. RESULTS: There was no statistically significant difference in bone uptake values, injected MDP doses or injection/examination time delay in any group. Cisplatin plasma values were significantly different in G2, G3, G4, and G5 (P < 0.05) but not in G1. CONCLUSIONS: Cisplatin chemotherapy seems to have no effect on the Tc-99m MDP uptake of normal bone.

Effect of D-penicillamine on rat lung elastin cross-linking during the perinatal period.

This study was designed to clarify the effects of D-penicillamine (DPA), a drug used for treatment of various pathological events, on lung elastin formation and maturation of the newborn in the perinatal period. The investigation was conducted on 20 newborn rats bred from 40 female and six male rats. DPA doses 400 mg kg(-1) day(-1) and physiological saline were given intraperitoneally (i.p) to experimental and control groups. To assess newborn maturation, their body and lung weights were determined. Serum Cu levels were measured by atomic absorption spectroscopy and ceruloplasmin (Cp) activities were measured spectrophotometrically. Newborn lung tissue elastin, desmosine (DES) and isodesmosine (IDES) levels were measured by HPLC. The results showed that DPA treatment caused loss of skin elasticity and reduction in body and lung weight in newborns of the experimental group. The serum Cu levels and Cp activity were found to be significantly lower in both maternal and newborn of the experimental groups compared with the control group. The lung DES, IDES and elastin values of newborns in the experimental group were decreased compared with the control group. In conclusion, our results indicate that 400 mg kg(-1) day(-1) DPA, a dose that is used in the treatment of Wilson's disease, rheumatoid arthritis and cystinuria, caused the retardation of newborn maturation, a decrease in DES-IDES cross-links and levels of lung elastin of offspring in the perinatal period. Another conclusion to be drawn from this study is that even low levels of Cu depletion due to DPA administration induces a change in cross-linking in lung elastin during the perinatal period.