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Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r = 0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.

Strontium kinetics were investigated in a group of 14 patients receiving 89Sr palliation for metastatic bone disease secondary to prostatic carcinoma. Using 85Sr as a tracer, total body strontium retention R(t) was monitored for a 3 month period following 89Sr administration, and at 90 days was found to vary from 11% to 88% and to correlate closely with the fraction of the skeleton showing scintigraphic evidence of osteoblastic metastatic involvement. Strontium renal plasma clearance varied from 1.6 l/day to 11.6 l/day, and in nine patients was significantly reduced compared with values found in healthy adult men, probably due to increased renal tubular reabsorption associated with the disturbance of calcium homoeostasis. Renal clearance rate was the principal factor determining R(t) for t less than 6 days, and was an important secondary factor at later times. Over the interval 30 days less than t less than 90 days, R(t) was closely fitted by the power law function R(t) = R30 (t/30)-b, with R30 and b showing the close correlation expected from the effect of R(t) on strontium recycling. The correction of the data for this effect to determine the true skeletal release rate is described. Measurement of localized strontium turnover in individual metastatic deposits from whole body profiles and scintigraphic images gave retention curves that typically rose to a plateau by 10 days after therapy, and then decreased very slowly. In contrast, retention curves for adjacent normal trabecular bone showed more rapid turnover, peaking at 1 day and subsequently decreasing following a t-0.2 power law function.(ABSTRACT TRUNCATED AT 250 WORDS)

In a prospective study of 201Tl-99mTc subtraction scintigraphy, 61 hyperparathyroid patients were investigated prior to neck exploration. At surgery, 46 adenomatous and 28 hyperplastic parathyroid glands were excised. We examined the relationship between the pathological category of these glands, their mass, uptake of 201Tl thallous chloride, and the frequency of true-positive and false-negative scintigraphic findings. The variation of sensitivity with parathyroid mass was found to be similar for both adenomatous and hyperplastic glands, with a detection threshold that lay in the range 0.3-0.8 g. The higher overall sensitivity for the detection of adenomas (85%) compared with hyperplasias (44%) was due to the smaller mean weight of the latter. When the parathyroid uptake of thallium was quantified scintigraphically, the practical detection limit of subtraction scanning was found to be an uptake of 0.015%. For glands greater than 1.5 g in weight, uptake increased linearly with mass, and specific uptakes were within the range 0.01-0.04%/g. Below lg, certain small glands had much higher specific uptakes, up to 0.2%/g. The range of specific uptakes found was similar for both adenomatous and hyperplastic categories. Multinodular or diffuse goitre was a cause of failure in 10% of investigations. In a further 5%, a solitary thyroid nodule gave rise to a false-positive result.

Strontium plasma clearance is an important factor determining the absorbed dose to metastases and bone marrow in patients receiving 89Sr radionuclide therapy for metastatic bone disease. Amongst male patients with disseminated prostatic carcinoma, the renal component of strontium clearance is frequently greatly reduced compared with values reported for healthy middle aged men. We report a study of renal and gut strontium plasma clearance, renal function, calcium urinary excretion, parathyroid function and extent of skeletal osteoblastic metastatic disease in patients referred for radiostrontium therapy for metastasised prostatic malignancy. The wide variation in net strontium clearance was principally due to variation in the renal component. Low values of strontium renal clearance were found to correlate with the elevation of serum PTH and nephrogenous cyclic AMP, which in turn correlated with extent of skeletal metastatic disease. This suggests that the osteosclerotic metastases characteristic of prostatic carcinoma induce secondary hyperparathyroidism due to the high avidity of the skeleton for calcium. The resulting reduction in strontium excretion may be beneficial to the objectives of radiostrontium therapy.

The total strontium plasma clearance rate due to excretion through the kidneys and gut has an important influence on the absorbed does delivered to skeletal metastases and red bone marrow in patients receiving 89Sr radionuclide therapy for disseminated prostatic carcinoma. Although a measurement of the renal strontium plasma clearance rate may readily be obtained through a 24-h urine collection, little information is available on the correlation between renal and total clearances. We describe a method of determining total strontium plasma clearance rate from whole body counter measurements of total body strontium retention and measurements of plasma strontium concentration following administration of a 85Sr tracer dose at the time of 89Sr therapy. Amongst the 26 patients whom we studied, the total clearance rate varied from 1.2-15.0 l/day, renal clearance rate from 0.1-11.5 l/day, and the mean gut clearance rate was 2.0 l/day. A close correlation was found between total and renal clearance, with the renal component accounting for 96% of the variance in total strontium plasma clearance. A weak collection may exist between gut and renal clearance.

Following a case report that oral nifedipine can suppress the secretion of noradrenaline by phaeochromocytoma, we examined the effect of nifedipine on the tumour kinetics of tracer 131I-meta-iodobenzylguanidine (131I-mIBG) in five patients referred for mIBG radionuclide therapy for disseminated malignant phaeochromocytoma. In one subject a striking modification of mIBG kinetics was found that resulted in a doubling of the absorbed dose to tumour while the patient was taking nifedipine. At the same time, urinary excretion of noradrenaline was suppressed by a factor of three. The effect of nifedipine in this patient was confirmed when tracer studies were repeated nine months later. The changes in tumour kinetics were shown to be due to prolonged retention of mIBG rather than increased tumour blood flow or alteration of the curve of mIBG plasma concentration as a function of time.

A new method for the diagnosis of venous occlusion involves three stages: first, injection of 99mTc-labelled fibrinogen into a distal vein in the suspected limb with a dynamic gamma scan of venous flow; second, a static pool scan of both limbs to show the anatomy of the veins seen in the dynamic scan and third, a later static scan showing 99mTc-fibrinogen associated with thrombus. In occlusion, absence of flow in the dynamic scan corresponds to the presence of isotope in thrombus in the second static scan. The test uses a low-volume, low-radioactivity injection and may be repeated many times.

We present dosimetry for spinal metastases and red bone marrow in two patients who received 89Sr therapy for disseminated prostatic carcinoma. Absorbed dose to metastases was estimated by combining 85Sr gamma camera studies with computed tomographic measurements of bone mass, and doses of 20 cGy/MBq and 24 cGy/MBq were found for vertebral metastases that uniformly involved the bodies of L3 and D12 respectively. Absorbed dose to red bone marrow was estimated from total body strontium retention studies using the ICRP model for bone dosimetry, and a ratio of metastatic to marrow dose of around 10 was found in each patient. Although they received comparable treatment activities of around 200 MBq, the patients showed markedly different haematological response, this difference being confirmed when each received a second 89Sr treatment 6 months after the first. As a result, clinically significant thrombocytopenia occurred in one patient which prevented further radiostrontium therapy being given.

We have recently reported evidence that the calcium antagonist nifedipine can improve the tumour retention of 131I-metaidobenzylguanidine (131I-MIBG) in patients with malignant phaeochromocytoma. During studies of the pharmacological modification of tumour MIBG kinetics, it is important to distinguish clearly between a direct effect on MIBG cellular retention by a pharmaceutical, and secondary effects due, for example, to a change in glomerular filtration rate (GFR). In order to provide the fundamental kinetic data required for the numerical modelling of the effect of nifedipine on tumour MIBG kinetics, we have investigated the influence of GFR on MIBG plasma and renal kinetics. The 123I-MIBG plasma curve and MIBG renal plasma clearance rate were studied in ten patients, ranging from subjects without biochemical or scintigraphic evidence of phaeochromocytoma to individuals with widely disseminated metastatic disease. GFR was measured using the 99mTc-DTPA plasma clearance method. In four cases, the studies were repeated with the patients taking oral nifedipine. Statistically significant correlations were found between GFR and the MIBG plasma concentration. MIBG renal plasma clearance rate and the early (0 to 5 min) renal excretion of MIBG. The data permit the evaluation of the plasma integral during the first few min following bolus injection, a quantity important in the numerical modelling of tumour kinetics. GFR was found to have a major influence on whole-body MIBG kinetics, but there was also evidence of the effect of the metastatic tumour burden.