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The requirements, problems and progress of radioimmunotherapy in the management of certain malignancies are described. The future prospects using a two- or three-stage approach are promising.

Ovarian Cancer is a debilitating disease. It usually presents in an advanced state and then requires radical surgery and repeated courses of chemotherapy.lt is the second most common cause of death due to cancer in women.

Adventure with the kidneys started at the Middlesex Hospital culminating in 1971 with Britton and Brown’s monograph Clinical Renography. and the team later cleaned up the renogram with Computer assisted blood background subtracted, CABBS, Renography etc. Clinicians and scientists from the UK have played a major and significant role in developments of radionuclide renal studies have an established place in Nephrology and Urology. This chapter explores the early days of radionuclide renal studies with special emphasis mainly to the work at St Bartholomew’s Hospital.

The monoclonal antibody PR1A3 against a normal colonic columnar cell surface antigen has been labelled with 99mTc and used for imaging colorectal cancer. High uptake in undifferentiated cancer is seen. The tumour to mucosa ratio was up to 63:1 and the percentage of the injected activity in the tumour up to 1.7 X 10(-2%)g-1. As 99mTc is continuously available in a Nuclear Medicine Department, on receipt of a request the study may be completed within 24 h enabling radioimmunoscintigraphy to be used routinely in the management of patients with colorectal cancer.

There is no simple analytical test. Radionuclide diuretic renography (RDR), being a dynamic imaging study reflecting the function of the kidney and the urodynamics of the urinary tracts, has the potential to predict the outcome of surgery in obstructive uropathy. In 12 sheep, we occluded one ureter for a maximum of seven weeks and followed up for a maxim of five weeks after release of occlusion. Repeated Tc-99m DTPA diuretic renography studies were performed and the results were correlated with the duration of complete ureteric occlusion. The renal uptake percentage and the extraction slope of the time activity curve (TAC) showed progressive and steady decrease over the period of the occlusion. By the fifth week there was very low uptake (less than 18%) and the TAC was almost flat, suggestive of severe nephropathy. The parenchymal transit time index (PTTI) showed immediate rise after occlusion but with no progressive increase in its value. By the fifth week it dropped down to normal. After release, the recovery of function showed good correlation with the renal uptake percentage and extraction slope of TAC before release of occlusion. Therefore both these parameters, rather than PTTI, can be used to predict the outcome of surgery before the release of complete obstruction of the ureter.

The value of non-invasive spleen scanning with 51Cr-chromate heat damaged red cells has been assessed in 68 patients with histologically proved Hodgkin's disease in whom pre-treatment laparotomy with splenectomy was performed. The scans were reported independently by two observers. Following this, the uptake pattern of the radioactive tracer and size of organ on the scan were compared with the post-operative weight and pathology of the spleen. From these results it is concluded that this method of spleen scanning is an unreliable technique in staging Hodgkin's disease.

A physical definition of renal blood flow in man is the volume flow of blood per unit time through a cross-section of the renal arteries. On this definition renal blood flow has never been measured in a normal person under normal conditions. Instead, each type of measurement has forced a definition of flow to be made in terms of the chosen method of measurement. Each measurement is considered to be endowed with meaning, and this meaning is then pursued. Although the search initially is for a ‘true’ measure of renal or intrarenal flow as an end in itself, the result is usually used by others to investigate some working hypothesis. In this way an operational definition is evolved: How is the intrarenal distribution of flow affected in the disorder under investigation and does it alter with treatment? Can one exclude/include a change in distribution of flow in a study of a particular disease? An operational definition implies a model representative of the system under study. The greater the distortion from physical reality that occurs on application of the model, the less acceptable is a measurement in the context of its usage. Lack of acceptability usually becomes evident when a technique which gives meaningful results in one context is extended to another, typically from a ‘normal’ to an ‘abnormal‘ situation. Smith (1951) defined ‘effective’ renal plasma flow (ERPF) in a circular way, as the flow to tubules which were completely efficient in extracting p-aminohippurate. Tubular secretion became indissolubly linked to renal plasma flow by this definition. This did not matter until it was required, for example, to study proximal tubular function independently of renal flow or, more particularly, the distribution of flow to the renal medulla. However, the model was stretched beyond acceptability when it was postulated that non-cortical flow could therefore be determined by the difference between

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.

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.

SUMMARY The interpretation of the renogram is not straightforward. This is due to the complexity of the kidney and not to any complexity in the technique of renography. The commonly used empirical method of interpretation is discussed. The technique of Computer Assisted Blood Background Subtraction (C.A.B.B.S.) renography is described and a theory of the renogram is presented which leads to a rigorous method of quantitation. The ratio between the efficiencies with which the kidneys take up Hippuran can be obtained. This is equivalent to the ratio of the effective renal plasma flows. It is hoped to quantitate aspects of the mechanism of transport of Hippuran through the kidney in order to assess renal autoregulation and other aspects of nephron function.

The 131I Hippuran renogram trace is impaired by the presence of extra-renal blood background. A method of blood background subtraction involving the use of a digital computer is introduced and examples of the use of the test are given in detecting unilateral renal artery stenosis and in the assessment of impaired renal function. Computer assisted blood background subtraction (C.A.B.B.S.) allows a more accurate estimation of the time to peak of the renogram. The time to peak depends on transit time and urine flow. C.A.B.B.S. allows the further analysis of the “nonfunctioning” standard renogram curve into those where up to 20 per cent of renal function is revealed and those with a “nephrectomy” trace. It increases the usefulness of renography performed in patients with uraemia and the results may have prognostic significance.

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.

Intrarenal plasma-flow distribution has been determined non-invasively in man. The reduction in effective renal plasma flow in essential hypertension is due to a reduction in flow to the cortical nephrons only; the juxtamedullary nephrons maintain their flow. A disorder of the autoregulatory control of cortical-nephron flow is postulated to be the genetic defect in essential hypertension.

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.

Summary Studies in animals have determined the importance of specific receptors to the action of many hormones and drugs. In man, a non-invasive external counting technique has been used and absence of receptor function has been demonstrated in a patient with nephrogenic diabetes insipidus using radioactively labelled arginine vasopressin. This is in contrast to the findings in a patient with pituitary diabetes insipidus and a normal control. These results suggest a model for the study of hormone and drug kinetics in man avoiding multiple samplings of biological fluids.

Eighteen patients with a history of previous anterior myocardial infarction and suspected left ventricular aneurysms were studied both by contrast left ventriculography and by first pass radionuclide ventriculography using Technetium99m and a computerised multicrystal gamma camera. The radionuclide study successfully identified all 14 patients with aneurysms and all 4 with diffusely hypo-kinetic ventricles. Ejection fraction calculated from the change in radioactive counts in the left ventricle correlated well with that calculated from the area-length method from the contrast angiogram (r = 0.83). Ventricular volumes calculated from the area-length formula for both contrast and radionuclide angiograms correlated closely (r = 0.85 and r = 0.89 for end-systolic and end-diastolic volumes, respectively). In the patients with aneurysms, there was a close correlation between the extent of akinesis, as assessed by the two methods (r = 0.94). The ability of the radionuclide ventriculogram to provide accurate information on global and segmental ventricular function, and to differentiate between segmental and diffuse ventricular dysfunction, enables the method to act as a screening procedure in the investigation of patients with suspected left ventricular aneurysms.

Summary 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.

Summary The ‘bootstrap’ model of the handling of salt, water and urea by the renal medulla is based on the concepts and data of Stephenson (1972), and Kokko and Rector (1972), and adds support to them. Revision of the traditional counter current hypothesis is necessary since active transport of salt and urea is absent from the inner medulla. This advanced model is structured appropriately and demonstrates how events in the medulla interact and vary with time as change from a diuretic to an antidiuretic state proceeds.

Probe renography is recognised to be unreliable in the diagnosis of upper urinary tract obstruction since a rising third phase may be seen for a number of different reasons. Even the presence of diminished function and a rising third phase is not reliable evidence of obstruction: A system which has been irreversibly damaged by an obstruction which has been relieved may remain capacious and will have the same appearance as a truly obstructed kidney. Diuresis renography has helped to overcome this problem (O’Reilly et al. 1978).