The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater Vss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the Cmax was 20 times lower than the C0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t1/2β ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the Vss and WBR were significantly correlated with serum alkaline phosphatase levels and the Vss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t1/2β after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher Vss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.

We have compared two "markers" in the follow up of post treatment (surgery and therapeutical use of I-131) differentiated thyroid carcinoma. In 153 patients, thyroglobulin (Tg) serum levels were measured after withdrawal of I-thyroxine therapy, before performing a whole-body scan (WBS) with iodine-131; in 55 of these patients, Tg was measured again after at least 45 days of I-thyroxine treatment. The patients were followed between 3 and 10 years, and there were 2713 matched studies. Our results indicate for both parameters, false positive and negative values; sensitivity (SE) for WBS was 89% and specificity (SP) 83%; Tg presents a SE of 86% and SP of 83%. Matching both parameters, SE was 95% and SP 98%. The causes of false results are discussed. Tg determinations under I-thyroxine treatment do not permit the establishment of absence of illness; 37.7% of patients with demonstrated metastases or relapse showed negative Tg values that reached pathological values after suspension of I-thyroxine treatment; another 41.4% with elevated Tg values under therapy reached these values after suspension of I-thyroxine. Both markers, when utilized at the same time, offer the best possibilities in the follow-up of differentiated thyroid carcinoma, when determinations are carried out after suspension of hormonal treatment.

We have investigated the possibilities of technetium-99m-(-3-aminohydroxypropylidene)-1-1-bisphosphon ate ([99mTc]APD) as a bone scanning agent in 14 normal subjects and 28 patients. Similar studies in the same normal subjects and patients were carried out with 99mTc-methylene-bisphosphonate ([99mTc]MDP). The compounds were labeled with 99mTc by means of an electrolytical method; the free pertechnetate content was always under 1%. The [99mTc]APD T1/2 of the third component of the disappearance plasma curve in six normal subjects was 152 +/- 46 min (mean +/- s.d.), while the 24-hr whole-body retention (WBR) was 17.6% +/- 4.6. The [99mTc]MDP value of the 24-hr WBR was 28.6% +/- 3.9 (p less than 0.001). The bone/soft-tissue ratio (B/ST) was investigated in eight control subjects on the eleventh thoracic and the fourth lumbar vertebrae. The B/ST ratios were similar for both APD and MDP studies. In 28 patients with suspected bone metastasis or primary bone disease, bone scintigraphy was carried out; both compounds showed similar findings and the same number of positive results. In five of these patients, the lesion/normal bone ratio was determined with values of 4.6 +/- 2.0 in APD studies and 4.8 +/- 2.3 with MDP. APD was also used in 126 patients; no adverse reactions were observed. The APD dose used i.v. for bone scanning was 200-fold less than those employed by mouth per day, for the treatment of bone disease for long periods. In our experience, APD appears to be an adequate agent for bone scintigraphy.