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The lack of equivalence in the distrubtion of normal ranges for free thyroxine index (FT4I) and free triiodothyronine index (FT3I) in the over sixty-five age-group, as compared with the fifteen-sixty-five age-group, supports the idea that "T4 toxicosis" is a common biochemical finding in elderly women. The disparity between FT4I and FT3I ranges was also reflected in the true free T4 and free T3 levels which were measured in some cases. These results suggest that when an increased FT4I is found in an elderly woman with cardiac disease, caution should be exercised in interpreting the result as indicating that thyrotoxicosis is the cause of the cardiac disorder. Estimation of total T3, FT3I, or free T3 seems useful in confirming euthyroidism in such cases.

Scintigraphy with 123I-radiolabeled metaiodobenzylguanidine (MIBG) was performed successfully in two patients with metastatic carcinoid tumor. The scintigraphic findings show diversity of the tumor deposits in the uptake of [123I]MIBG in the same patient and between patients.

A method for preparing meta-iodobenzyl guanidine (MIBG) labelled with 123I is described. This compound clearly imaged the normal adrenal medulla in seven out of eight patients with hypertension. The sites of metastases were demonstrated in two patients with malignant phaeochromocytoma.

Iodine-123 metaiodobenzylguanidine (MIBG) has been used as a diagnostic agent for imaging neural crest tumours. In a retrospective study of 27 patients, the role of 123I MIBG scintigraphy and X-ray computed tomography (CT) for detection of disease was compared. Both imaging techniques were accurate in the identification of these tumours. Iodine-123 MIBG was slightly more accurate in detecting metastatic disease. Computed tomography of tumours was useful in planning appropriate metastatic intervention. We suggest 123I MIBG should be the primary imaging procedure followed by CT in the investigation of these patients.

Forty-two patients were evaluated pre- and postextracorporeal shock wave lithotripsy (ESWL) using [99mTc]DTPA renography. A quantitative evaluation showed that the relative renal function decreased 2-3 days post-ESWL on the treated side, and the parenchymal transit time index (PTTI) increased 2-3 days post-ESWL (p less than 0.001) on the treated side and returned to the pretreatment level by 3 wk post-ESWL. The untreated side showed an increase in PTTI 2-3 days post-ESWL (p less than 0.01), which returned to normal by 3 wk post-ESWL. A significantly greater increase in PTTI was seen in patients who received greater than 1,000 shocks as compared with those who received less than 1,000 shocks. Five patients developed obstructing uropathy post-ESWL, when stone fragments caused ureteric obstruction.

The results of quantitative adrenal imaging using 75Se selenomethylcholesterol in sixty-two subjects are analysed. The adrenal area was localized by a renal scan, lateral views of which enabled adrenal depth to be estimated. The first nineteen cases were scanned with a rectilinear scanner and the remaining forty-three cases imaged with a gamma camera. Quantitation of adrenal uptake was performed on computer-stored static images obtained 7 and 14 days post-injection of 75Se selenomethylcholesterol (3 and 6 days in the first ten cases studied). Normal uptake was found to be 0.07-0.30% of the administered dose. Overall predictive accuracy of the type of adrenal disorder of thirty-two patients with Cushing's syndrome ws 90.6%, this included twelve cases of Cushing's disease (mean uptake 0.58%), seven ectopic ACTH syndromes (mean uptake 0.69%), five unilateral adenomata (mean uptake 0.93%), three post adrenalectomy regrowths (mean uptake 1.37%), three adrenal carcinomas (mean uptake 0.01%), one congenital hyperplasia (mean uptake 3.4%) and one unilateral nodular hyperplasia. Overall predictive accuracy of the cause of Conn's syndrome in twenty-two cases was 86.4%; this included thirteen cases of bilateral hyperplasia (mean uptake 0.34%), eight unilateral adenomata (mean uptake 0.47%) and one patient with mineralocorticoid excess in whom the cause has not been confirmed. The mean uptake in the normal adrenal in cases of unilateral adenoma was 0.19% (range 0.07-0.30%). Causes of unsatisfactory adrenal imaging are examined. The procedure is recommended as the localizing and lateralizing technique of choice in Cushing's syndrome except where due to adrenal carcinoma, and as an important non-invasive technique in Conn's syndrome for the lateralization of adenoma.

The early detection of metastatic spread in sixteen patients with osteosarcoma has been studied over a twelve month period, comparing the techniques of bone scanning and radiography. In only two patients were we able to demonstrate changes suggestive of pulmonary metastases any earlier with a 99mTc-EHDP scan than with chest radiographs and one of these resolved spontaneously. However, the bone scan did accurately delineate the extent of the primary tumour and may, therefore, be helpful in deciding the level of the amputation and the response of the patient to treatment, particularly now that chemotherapy and immunotherapy are frequently used in the management of the disease.

A study was undertaken to evaluate the role of positive infarct scintigraphy in the diagnosis of acute myocardial infarction (AMI), using Technetium99m stannous pyrophosphate (Tc-PYP) and a portable gamma camera. Sixty-one patients admitted to the Coronary Care Unit (CCU) with a presumptive diagnosis of AMI or ischaemic cardiac pain were studied. Positive scans were present in 24/25 (96%) patients with AMI and new Q waves, and in 10/12 (83%) patients with AMI and no Q waves. Nine of eleven (82%) patients with chest pain and no infarction had negative scans. Of thirteen patients with unstable angina, ten (77%) had positive scans. A further eight patients undergoing coronary artery bypass surgery for angina pectoris were studied pre- and postoperatively. Two patients had strongly positive postoperative scans. The Tc-PYP scan is valuable in the detection of peri-operative infarction following coronary artery surgery, and in patients with unstable angina the technique may detect small amounts of myocardial necrosis undetectable by more conventional means. When the diagnosis of infarction is obvious from the ECG, enzymes, or a combination of the two, the Tc-PYP scan provides no extra information helpful in patient management.

The percentage uptake of [123I]metaiodobenzylguanidine (MIBG) by tumors of the paraganglion system is compared with the number of neurosecretory granules (assessed by both light and electron microscopy) in the subsequently resected tumors in six patients. Iodine-123 MIBG was injected intravenously; the tumor uptake of [123I]MIBG varied between 0.001% and 0.14% of the injected dose per gram of tumor tissue at 22 hr. The number of neurosecretory granules in tissue sections was scored on a scale of I-III. A direct proportional correlation was found between the percentage uptake of [123I]MIBG by the tumor and the number of neurosecretory granules in the tissue sections but not with plasma or urinary catecholamines. This technique for imaging reflects the storage status of the tumor better than plasma and urinary catecholamine measurements.

A Phase I study in 12 patients with renal disorders compared the simultaneous clearances of 99mTc-labeled mercaptoacetyltriglycine (MAG3) and 131I-labeled orthoiodohippurate (OIH). The ratio of MAG3 to OIH clearance was 0.61 +/- 0.08 as a result of its smaller volume of distribution, ratio 0.65 +/- 0.09, for the clearance half-lives were similar, ratio 1.09 +/- 0.12. A Phase II study performed serially in 20 patients with equal doses of [99mTc]MAG3 and [123I]OIH gave images of equal quality. The relative renal functions were highly correlated (r = 0.97, p less than 0.001) and transit time analyses gave good correlations: parenchymal transit time index r = 0.81, p less than 0.05. We conclude that [99mTc]MAG3 has some advantages over [99mTc]DTPA and is a suitable replacement for [123I]hippuran in routine renal imaging, relative function, and transit time studies, but not for the accurate estimation of the renal plasma flow.

A technique is described for measuring an index of cardiac output, total and individual renal plasma flow, cortical and juxtamedullary nephron flow non-invasively in man with a single injection of 123I-o-iodohippurate. Ibopamine, a dopamine analogue, was administered orally, 200 and 600 mg, in a double-blind, placebo-controlled cross-over study in 6 healthy subjects. No change in pulse, blood pressure, cardiac output, urea, creatinine or electrolytes was seen. Ibopamine reduced effective renal plasma flow and cortical nephron flow and increased urine flow significantly. This may be due to differential vasoconstrictor and vasodilator effects on the two populations of nephrons. Indoramin, and alpha-1 postsynaptic adrenoceptor blocker, was administered orally, 50 mg, in a double-blind, placebo-controlled cross-over study in 14 healthy young males. No change in pulse, cardiac output, urea, creatinine or electrolytes was seen. Indoramin significantly reduced upright but not supine blood pressure and significantly increased effective renal plasma flow. Cortical nephron flow and juxtamedullary nephron flow tended to rise. Plasma renin activity was significantly elevated although there was no change in urinary sodium output. The effect of drugs on intrarenal blood flow distribution may be relevant to the management of essential hypertension.

It can be difficult to distinguish between various forms of pale intraocular tumour, and in particular between an amelanotic malignant melanoma, a choroidal haemangioma, and a solitary metastasis. If a monoclonal antibody specific for melanoma could be identified, it might be radiolabelled to provide a scanning technique which could distinguish between an ocular melanoma and a similar lesion. This pilot, in vitro study was undertaken to determine if monoclonal antibody against cutaneous melanoma recognises any antigenic similarity in ocular melanomas. Three cutaneous melanoma MoAbs 225.28S, 376.96S, and 763-24T and a non-specific MoAb HMFG2 were studied. Cell impressions were obtained from fresh ocular malignant melanomas. Standard staining techniques with immunofluorescence were used. MoAb 225.28S, 376.96S, and 763.24T were positive in melanomas with a dominant epithelioid cell type and in those with a dominant spindle cell type. It is concluded that MoAb 225.28S, 376.96S, and 763.24T may be suitable for imaging ocular melanomas after labelling with 123I, 111In, or 99mTc.

Radioiodinated metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes to image neural crest tumors. We report the uptake of 123I MIBG in a child with ectopic intracranial retinoblastoma. It is felt that 123I MIBG scintigraphy may have a role in detecting occult metastatic disease in these patients.

Renal and intrarenal distribution of flow together with an index of cardiac output is measurable using a single injection of 123I-o-iodohippurate. The argument is presented that in the treatment of essential hypertension one should avoid using drugs that reduce renal blood flow, a property of chronic therapy with most beta-blockers or diuretics. Reduction of renal blood flow is a stimulus to salt retention and renin release which tend to maintain hypertension. Drugs which increase renal blood flow, thereby augmenting the renal loss of salt and decreasing renin release, tend to reduce hypertension in the long term.

Since inert gas washout techniques for cerebral blood flow (CBF) measurement are not applicable to asymmetrical pathological states where assumptions about constancy of distribution, volume, and partition coefficients cannot be held to be valid, a new approach to regional and global CBF is described. Regional volume and regional mean transit time are measured independently to give regional volume flow in ml/min. In a pilot study, this noninvasive, quantitative technique has been applied to 37 patients with various clinical responses to subarachnoid hemorrhage. Global CBF and clinical grading were significantly associated. Reduction of regional CBF and spasm of the relevant arterial supply were also significantly associated in these patients.

The localization of i.p. injected, radioiodine conjugated monoclonal antibody HMFG2 was studied in 18 patients with ovarian carcinoma. Patients were injected i.p. at time points up to 168 h before laparotomy, at which time tumor, ascites, normal tissue, and blood samples were removed and the contained radioactivity measured. In the first 10 patients, localization was compared with that of a simultaneously injected irrelevant (nonspecific) antibody (UJ13A) of the same immunoglobulin class and, in the subsequent 8 patients, with HMFG2 administered i.v. After i.p. injection, HMFG2-radioiodine was found in concentrations of 0.0001-0.0030% of the injected amount per gram in solid tumor, 0.0363-0.02560%/g in ascites, 0.0003-0.0017%/g in blood, and 0.001-0.0012%/g in normal tissue. Tumor:normal tissue ratios of 0.9-10.0 and tumor:blood ratios of 0.3-4.0 were seen up to 168 h after injection. Localization of the HMFG2 conjugate was consistently greater than that of the irrelevant antibody. For solid tumor, the i.v. route of administration resulted in consistently higher absolute levels of HMFG2 conjugate uptake but tumor:blood and tumor:normal tissue ratios were similar. On the other hand the i.p. route of administration offered consistent advantages of 4- to 71-fold over the i.v. route when HMFG2 conjugate localization on ascites cells was examined. Ascites:normal tissue and ascites:blood ratios of up to 512 and 448, respectively, were achieved. After i.p. injection, radioiodine was cleared from the body exponentially with a half-life of 50 h. Maximum circulating blood levels of 8.6 +/- 2.0% injected activity were seen at 48 h and these then decreased with a t 1/2 value of 38 h. Over 80% of injected activity was cleared in the urine as nonprotein bound iodine by 168 h.

123I metaiodobenzylguanidine (MIBG) is a radiopharmaceutical used for imaging neural crest tumours. The possibility of using 123I MIBG for imaging retinoblastomas has been assessed in this pilot study. Ten patients were studied, nine with clinically and histologically proved retinoblastomas and one with Coats's disease. 123I MIBG scintigraphy correctly identified the neoplasm in eight patients but gave a negative result in two, one of whom had Coats's disease and the other a retinoblastoma which proved to be extensively necrotic on histological examination. These preliminary results suggest that 123I MIBG scintigraphy may have a role in differentiating retinoblastomas from lesions that simulate them.

Nineteen patients with unilateral cerebrovascular disease underwent cerebral blood flow (CBF) measurements; ten had been receiving conventional therapy and then were studied after treatment with captopril without or with a diuretic and nine on conventional therapy were studied twice as a control group. CBF (ml min-1) was measured after an intravenous injection of 99Tcm-labelled patient's red cells with a computer linked gamma camera over the vertex and a probe over the aorta. With deconvolution analysis regional CBF is given by regional cerebral volume divided by regional mean transit time. Results in the captopril group showed on average a 10% fall in mean blood pressure and a 10% rise in blood flow to the affected hemisphere. In the control group there was on average a 4% fall in pressure, together with an 11% fall in CBF to the affected hemisphere. Captopril appears to maintain autoregulation in cerebrovascular disease.

Primary hyperaldosteronism is a potentially curable cause of hypertension, and much interest has been shown in methods of diagnosing the associated hypokalaemic hypertension and localising the adrenal adenoma. In two patients the diagnosis of primary aldosteronism was confirmed by colonic potential measurement and the adenoma localised by a new subtraction technique for early adrenal imaging applied to the use of 131I-19-iodocholesterol. Both patients underwent adrenalectomy and in each case an adenoma was removed. Blood pressure and electrolyte levels returned to normal after operation. In one patient bilateral adrenal phlebography had failed to show the tumour, and sampling of aldosterone concentrations in the adrenal veins had been unsatisfactory.

The concept of decision-aiding ranges were introduced to improve diagnostic efficiency. The clinical uncertainty in distinguishing borderline cases of hyperthyroidism and hypothyroidism among 1559 consecutive requests for thyroid function tests was 47%. This was reduced to 22% by using the free thyroxine index and to under 2% by using specific tests determined by the decision-aiding ranges.

Radioiodinated I-123 metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes for detection of apudomas. In this paper normal physiological uptake of I-123 MIBG by the uterus during the menstrual phase of the uterine cycle is reported. It is likely that I-123 MIBG can be used to evaluate some of the problems in this context.

1. A new method, based on the transit time of omicron-iodohippurate sodium (Hippuran) through the kidney, is proposed as an accurate non-invasive means of measuring the intrarenal flow distribution in man. 2. Data from [123I]Hippuran gamma-camera renography are utilized in this method which employs region of interest selection, deconvolution, cross-correlation and curve subtraction to obtain the spectrum of transit times through the cortical and juxtamedullary nephrons. 3. In 12 normal subjects the mean percentage cortical flow was 83.9% (SEM 0.7%) which is approximately the anatomical proportion of cortical nephrons in the human kidney. 4. Cortical flow as a percentage of total was significantly reduced in 21 hypertensive patients, all of whom had no evidence of primary renal disease (mean 74.6%, SEM 1.5%). 5. In both the normotensive and hypertensive groups there was a good correlation between the results obtained from the left and right kidneys of the same patient showing the parallel physiological response of the two kidneys (mean difference 4%, P less than 0.001). 6. Reduction in the distribution of flow to the cortical nephrons in the essential hypertensive patients supports the hypothesis that renal autoregulation is important in this syndrome.

Monoclonal antibodies to epithelial cells, antigenic determinants labelled with I123 and I125, were administered to 10 immunodeficient mice bearing subcutaneous xenografts of human ovarian cancer. Radio scans of the body taken with a gamma camera at various time intervals demonstrated the presence of the cancer in all the mice. The smallest detectable tumor was approximately 1 mm in diameter. In a subsequent clinical study using 123I-labelled monoclonal antibodies in 10 patients with ovarian cancer, tumor detection was achieved in 8 patients, with tumor uptake of labelled antibody ranging between 0.2-2.6%. As a complementary method to existing forms of diagnosis, the targeting of monoclonal antibodies to ovarian cancer cells in vivo raises the hope of achieving early diagnosis in otherwise undetectable ovarian cancer, and provides encouragement to the concept of selective therapy in oncology.

It was considered that the first dose reaction occurring with prazosin may have been due either to hypotension or to a specific reduction in cerebral blood flow. The development of a quantitative non-invasion nuclear medicine technique for cerebral flow has now made it possible to investigate the effects of prazosin on cerebral blood flow in hypertensive patients. This double-blind study showed a significant decrease in BP and a small just significant increase in cerebral blood flow following a single 1-mg dose of prazosin, when compared with a placebo. From these results, it is unlikely that the first dose reactions which occurred with prazosin were due to a specific reduction in cerebral blood flow.

In September 1985 a task group on the clinical utility of labelled antibodies was founded by the Society of Nuclear Medicine - Europe. This document was elaborated to report the aims and the programs of the group. In September 1986 the European Nuclear Medicine Society decided to participate in this initiative and a joint task group was created. INITIAL DOCUMENT: A. The aims to the Task Group are to monitor, co-ordinate and promote research and clinical application of techniques using radiolabelled antibodies in nuclear medicine. A.1. The Group should develop into a major point of reference, giving scientific and technical support to each member of the Society involved in this field. B. To pursue these purposes it will be necessary to develop the following: B.1. Criteria to evaluate the suitability of antigen-antibody systems for tumour detection and/or therapy. B.2. Criteria for quality control of radioimmunoreagents. B.3. Criteria for the prevention of adverse reactions or damage due to the reagent. B.4. Selection of suitable dosimetric methods for diagnostic or therapeutic applications. B.5. Elaboration of protocols for clinical experiments, including appropriate techniques to be applied in single cases. B.6. Organization of cooperative studies. C. The Task Group should promote: C.1. Informal meetings between the members of the Group. C.2. Workshops open to the members of the Society and other researchers. C.3. Publication of reports in appropriate journals.

In 20 patients with pelvi-ureteric junction obstruction the results of quantification of the change in renal pelvis size during high-dose intravenous urography with a diuretic, pressure/flow studies, standard renography and deconvolution analysis of the gamma camera renogram have been compared. The results of high-dose intravenous urography and pressure/flow studies correlated well. Renography was unreliable in diagnosing obstruction unless deconvolution analysis of the gamma camera renogram was used to differentiate those showing an obstructive uropathy from those with an obstructing nephropathy.

1. The spectrum of transit times of sodium o-iodohippurate (Hippuran) through the kidney can be derived from an 131I- (or 123I-) labelled Hippuran renogram by deconvolution. In the rabbit and pig, as has previously been shown in man, the frequency distribution curve for the transit times was bimodal. Since the transit time is likely to be proportional to the nephron length, the area of the first mode is likely to represent plasma flow to the shorter outer cortical nephrons whereas the delayed mode represents flow to the long juxtamedullary nephrons. 2. This interpretation was tested by simultaneously comparing renography with the microsphere method of measuring intrarenal plasma flow distribution in 12 rabbits and two pigs with a variety of anaesthetics. A close agreement was found between both methods for the percentage of plasma flow distributed to the outer cortical nephrons, thus supporting the use of "transit renography" to determine the intrarenal distribution of plasma flow.

99Tcm (+/-)-hexamethylpropyleneamineoxime (HMPAO) (99Tcm Hexametazime) has been recently reported as an alternative for labelling leucocytes. For reasons of convenience, radiation dose and image quality, many workers have welcomed this novel approach except for its complicated labelling protocol and venesection of 100 ml. This technique has been modified to give a simpler routine in-house labelling technique. It has three advantages: only about 20 ml of blood is required, the labelling time is just under 1 h and high yields of labelled leucocytes are obtained (mean of 500 MBq per injection dose). The properties of labelled leucocytes using this modified method are; 80% granulocyte-bound radioactivity, a rapid lung transit and a blood granulocyte recovery of 40% at 30 min similar to those described previously. The viability of the labelled leucocytes was tested and confirmed in vitro using a migration technique and in vivo by showing no lung retention on early imaging and high splenic uptake. A rapid in-process chromatography assessment procedure for regulating the protocol has been developed. Successful abscess imaging by 4 h has been achieved in 21 patients with normal results in another 22 patients without abscesses. This simpler method should encourage a more widespread application of scintigraphy using radiolabelled granulocytes.

Sixty-three patients presenting with the clinical problem of renal outflow disorder were studied using 99mTc DTPA. The techniques of frusemide diuresis and parenchymal transit time index analysis were compared and both shown to be successful in aiding the decision as to the presence or absence of significant outflow obstruction.

A simplified technique of labelling leucocytes with technetium-99m is described and applied to patients with active rheumatoid arthritis. The clinically active and less active knees in seven patients were imaged and the uptake of labelled leucocytes was measured. The measurements were repeated after local steroid injection into nine painful knees. A 50-80% reduction in leucocyte uptake localized to the region of the synovium was demonstrated in the eight knees which showed clinical responses and a rise of 8% in the non-responder. There was a variable response in the knees that were not injected. 99Tcm leucocyte imaging in rheumatoid arthritis is able to assess objectively joint inflammation and its response to treatment.

A monoclonal antibody HMFG2 labeled with iodine 123 (123I) was given to a patient who had ovarian cancer. The scan taken 18 hours after administration of the antibody demonstrated the presence and the position of residual tumor in the pelvis that was not previously detected by ultrasonography and computerized tomography (CT) scanning. The presence of tumor was confirmed by surgery and histologic as well as immunoperoxidase examination of resected tissues. The tumor mass found was less than 0.8 cm in diameter. It is concluded that, in the search for residual or early ovarian cancer in the pelvis, monoclonal antibody scanning using 123I-labeled HMFG2 can complement ultrasonography and CT scanning.