Optimal treatment of painful bone metastases with Samarium EDTMP in a haemodialysis patient: effectiveness and safety of internal radiotherapy.

One of the current therapeutic approaches in the treatment of osteoblastic bone metastases uses the affinity of Samarium ((153)Sm) ethylene-diamine-tetramethylene phosphonic acid (EDTMP) for bone areas of bone turnover. As Samarium EDTMP is a beta-emitter, the radiotherapy contributes to osteoblastic bone lesion control over time. To date, the safety and effectiveness of Samarium therapy have not been established in patients with renal impairment. In this first report, we describe our experience of use of Samarium EDTMP in conjunction with biphosphonates in a haemodialysis patient for treatment of painful bone metastasis. Encouraging results were obtained in achieving pain control. The use of this radioisotope could be more widely applied to treat haemodialysis patients.

Significance of low levels of thyroglobulin in fine needle aspirates from cervical lymph nodes of patients with a history of differentiated thyroid cancer.

OBJECTIVE: Measurement of thyroglobulin in the washout of lymph node (LN) fine needle aspirates is recommended in the follow-up of patients with differentiated thyroid cancer (DTC). The significance of low fine needle aspirates thyroglobin (FNATg) levels remains a question, which we addressed. METHOD: Prospective study comparing FNATg with FNA cytology. Exploration of 34 DTC patients (53 cervical LNs), 26 non-thyroidectomized patients with a thyroid-unrelated cervical mass (negative controls) and 13 with 21 thyroid nodules (positive controls). The 12 DTC patients (19 LNs) with a malignant FNA cytology and/or high FNATg level received LN surgery (11 patients) or I(131)-iodine treatment (1 patient) and the outcome measure was pathological or scintigraphic evidence of DTC LN metastasis. RESULTS: All 26 negative controls showed FNATg <1 ng/FNA and all 21 positive controls showed high levels of FNATg (127-210,000 ng/FNA, median 38,000). Among DTC patients in 25 LNs with a benign FNA cytology, FNATg was undetectable in 24 and low in 1 (6 ng/FNA); in 19 LNs with a malignant FNA cytology, FNATg was high in 17 (80-140,000 ng/FNA, median 7174 ng/FNA) and low in 2 (6.6 and 7.1 ng/FNA), which proved to be low Tg immunostaining oncocytic DTC metastasis; in 9 LNs with a non-informative cytology, FNATg was undetectable in 8 but 11,825 ng/FNA in 1, which proved a DTC metastasis. Measurement of FNA albumin demonstrated that contamination of FNA by serum proteins was negligible. CONCLUSION: Low FNATg levels can indicate a DTC metastasis. It cannot be related to clinically relevant levels of serum Tg.

Cellular uptake of (99m)TcN-NOET in human leukaemic HL-60 cells is related to calcium channel activation and cell proliferation.

PURPOSE: A major goal of nuclear oncology is the development of new radiolabelled tracers as proliferation markers. Intracellular calcium waves play a fundamental role in the course of the cell cycle. These waves occur in non-excitable tumour cells via store-operated calcium channels (SOCCs). Bis(N-ethoxy, N-ethyldithiocarbamato) nitrido technetium (V)-99m ((99m)TcN-NOET) has been shown to interact with L-type voltage-operated calcium channels (VOCCs) in cultured cardiomyocytes. Considering the analogy between VOCCs and SOCCs, we sought to determine whether (99m)TcN-NOET also binds to activated SOCCs in tumour cells in order to clarify the potential value of this tracer as a proliferation marker. METHODS: Uptake kinetics of (99m)TcN-NOET were measured in human leukaemic HL-60 cells over 60 min and the effect of several calcium channel modulators on 1-min tracer uptake was studied. The uptake kinetics of (99m)TcN-NOET were compared both with the variations of cytosolic free calcium concentration measured by indo-1/AM and with the variations in the SG2M cellular proliferation index. RESULTS: All calcium channel inhibitors significantly decreased the cellular uptake of (99m)TcN-NOET whereas the activator thapsigargin induced a significant 10% increase. In parallel, SOCC activation by thapsigargin, as measured using the indo-1/AM probe, was inhibited by nicardipine. These results indicate that the uptake of (99m)TcN-NOET is related to the activation of SOCCs. Finally, a correlation was observed between the tracer uptake and variations in the proliferation index SG2M. CONCLUSION: The uptake of (99m)TcN-NOET seems to be related to SOCC activation and to cell proliferation in HL-60 cells. These results indicate that (99m)TcN-NOET might be a marker of cell proliferation.

Control of erythropoiesis after high altitude acclimatization.

Erythropoiesis was studied in 11 subjects submitted to a 4-h hypoxia (HH) in a hypobaric chamber (4,500 m, barometric pressure 58.9 kPa) both before and after a 3-week sojourn in the Andes. On return to sea level, increased red blood cells (+3.27%), packed cell volume (+4.76%), haemoglobin (+6.55%) ( P<0.05), and increased arterial partial pressure of oxygen (+8.56%), arterial oxygen saturation (+7.40%) and arterial oxygen blood content ( C(a)O(2)) (+12.93%) at the end of HH ( P<0.05) attested high altitude acclimatization. Reticulocytes increased during HH after the sojourn only (+36.8% vs +17.9%, P<0.01) indicating a probable higher reticulocyte release and/or production despite decreased serum erythropoietin (EPO) concentrations (-46%, P<0.01). Hormones (thyroid, catecholamines and cortisol), iron status (serum iron, ferritin, transferrin and haptoglobin) and renal function (creatinine, renal, osmolar and free-water clearances) did not significantly vary (except for lower thyroid stimulating hormone at sea level, P<0.01). Levels of 2,3-diphosphoglycerate (2,3-DPG) increased throughout HH on return (+14.7%, P<0.05) and an inverse linear relationship was found between 2,3-DPG and EPO at the end of HH after the sojourn only ( r=-0.66, P<0.03). Inverse linear relationships were also found between C(a)O(2) and EPO at the end of HH before ( r=-0.63, P<0.05) and after the sojourn ( r=-0.60, P=0.05) with identical slopes but different ordinates at the origin, suggesting that the sensitivity but not the gain of the EPO response to hypoxia was modified by altitude acclimatization. Higher 2,3-DPG levels could partly explain this decreased sensitivity of the EPO response to hypoxia. In conclusion, we show that altitude acclimatization modifies the control of erythropoiesis not only at sea level, but also during a subsequent hypoxia.