D. M. Ackery

A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone

The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).

Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate.

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<6 days, and was an important secondary factor at later times. Over the interval 30 days t<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. The changes in strontium kinetics found in metastatic bone disease are favourable to the objectives of 89Sr therapy.

Strontium-89 chloride for pain palliation in prostatic skeletal malignancy

In a multi-centre study strontium-89 was shown to be effective in relieving bone pain from prostatic carcinoma in patients who had failed conventional therapies. Of 83 patients assessed at 3 months, following the administration of a dose of at least 1.5 MBq/kg, 75% derived benefit and 22% became pain free. Symptomatic improvement usually occurred within 6 weeks and continued for between 4 and 15 months (mean 6 months). Based on the dose estimation part of this study the recommended dose of strontium-89 is 150 MBq. Toxicity was low, provided platelet levels were above 100 x 10(9) l-1 at the time of treatment. Repeat treatments with strontium-89 may be given at intervals of not less than 3 months. Strontium-89 is administered intravenously on an out-patient basis with no special radiological protection precautions.

Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid

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.

Deconvolution analysis of the scintillation camera renogram

A scintillation camera with digital data store has been used to assess renal function. Analysis of the renogram by deconvolution, using an on-line digital computer, shows promise as a means of expressing renal function in terms of tubular transit times for 123I-Hippuran.

Dosimetry of iodine 131 metaiodobenzylguanidine for treatment of resistant neuroblastoma: results of a UK study

In 1987, the United Kingdom Childrens Cancer Study Group (UKCCSG) set up a multi-centre study to investigate the toxicity of iodine 131 metaiodobenzyl-guanidine (mIBG) in the treatment of resistant neuroblastoma. Since December 1987, 25 children suffering from neuroblastoma have been treated with131I-mIBG at six UK centres. All centres followed standardised physics and clinical protocols to provide consistent toxicity and dosimetry data. These protocols describe the methods employed for both the tracer study using131I-mIBG and the subsequent therapy. Whole-body dosimetry calculations were performed on data from the tracer study. The activity administered for therapy was the amount predicted to deliver a predefined whole-body dose. Estimates of doses delivered to various organs during treatment are given in Table 1.

New approach to the localisation of phaeochromocytoma: imaging with iodine-131-meta-iodobenzylguanidine.

Thirty eight patients with known or suspected phaeochromocytoma were studied by radioisotope imaging after intravenous administration of iodine-131-meta- iodobenzylguanidine (131I- mIBG ), a radiopharmaceutical which has affinity for chromaffin tumours. Seventeen positive results (including one false positive) and 21 negative results (including two false negatives) were obtained. Clinical accuracy was 92%. Urinary noradrenaline concentrations were raised in all patients with confirmed phaeochromocytoma. These findings show that 131I- mIBG is of value in localising and assessing the extent of chromaffin tumours.

Assessment of progression of secondary bone lesions following cancer of the breast or prostate using serial radionuclide imaging

A serial study on 32 patients with bone metastases following cancer of the breast or prostate was performed over three years. Up to ten sets of images (average of four) per patient were obtained during this period using 99Tcm methylene diphosphonate as the radiopharmaceutical. Ninety-three paired serial images of individual lesions were qualitatively assessed for change by three physicians in nuclear medicine and the results were compared with the quantitative results from computer analysis. The reproducibility of the quantitative approach was determined by the analysis of 20 paired lesions by three physicists. It was found that quantitative changes in uptake of less than 20% between images were generally not detected by the medical observers; a change of 41% had only a 95% probability of being identified as change by the physicians. Although much more reproducible in determining changes in individual lesions, the quantitative approach was found to be inferior to the qualitative assessment of overall change in the majority of cases which involve multiple lesions. The basic assumption that uptake varies proportionally with progression of the bone lesion is discussed an is considered in some instances to be untenable. The conclusion is drawn that the determination of progression from changes of uptake in longstanding lesions is uncertain and is subsidiary in importance to the detection of new lesions.

Strontium-89 radionuclide therapy: a dosimetric study using impulse response function analysis

In a series of patients receiving 89Sr palliation for metastasised prostatic carcinoma, strontium renal plasma clearance was found to vary from 0.14 to 11.81 day-1, and the extent of skeletal metastatic disease seen on 99Tcm-MDP images varied from a few small metastases to a superscan. Using a numerical technique based on impulse response function (IRF) analysis, we have investigated the effect of such variation between patients on 89Sr dosimetry. The whole-body IRF, HWB(t), is defined by the deconvolution of the whole-body strontium retention function, RWB(t), with the plasma retention function, P(t). For patients with minimal metastatic bone disease we assumed HWB(t) = HO(t), where HO is the IRF derived from the International Commission on Radiological Protection model for normal strontium metabolism. The strontium plasma clearance, k, was allowed to vary, and the resulting variation of RWB(t), P(t) and absorbed dose to bone marrow calculated. By convoluting P(t,k) with the IRF measured for a discrete metastasis, the effect of varying k on tumour dose was investigated. Tumour and bone marrow dose were shown to change by a factor of three as k varied over the range observed in patients. For patients with extensive metastatic bone disease we assumed HWB(t) = (1-beta)HO(t) + beta HS(t), where HS was the IRF measured for a superscan patient and beta was a parameter reflecting the extent of skeletal metastatic disease. The effect of varying beta on tumour and bone marrow dose was investigated, and dose shown to decrease by a factor of five as beta increased from zero to unity. Impulse response function analysis was found to be a powerful and useful aid in clarifying the relationship between strontium kinetics and 89Sr dosimetry.

Disseminated malignant phaeochromocytoma: localisation with iodine-131-labelled meta-iodobenzylguanidine.

Meta-iodobenzylguanidine, a guanethidine analogue, is a newly synthesised substance capable of imaging the adrenal medulla. In a woman in whom phaeochromocytoma has been diagnosed iodine-131-labelled metaiodobenzylguanidine was given intravenously; gamma-camera images showed bilateral adrenal tumours and uptake corresponding to bone and liver metastases. 131I-meta-iodobenzylguanidine is effective in localising phaeochromocytomas, and the technique is safe, specific, and non-invasive.