Radiation exposure to comforters and carers during paediatric molecular radiotherapy.

BACKGROUND: To show whether the incidental radiation exposure received by comforters and carers of children undergoing molecular radiotherapy was kept as low as reasonably achievable and was within English national dose constraints. PROCEDURE: The radiation exposure of adult comforters and carers was routinely monitored with a whole body personal dose meter while the child was in hospital. Data were collected on iodine-131 meta-iodobenzylguanidine (131 I-mIBG), lutetium-177 DOTATATE (177 Lu-DOTATATE), and iodine-131 sodium iodide (131 I-NaI) treatments. RESULTS: Data were available for 50 treatments with high-administered activity double-infusion 131 I-mIBG and 12 single administrations; 15 177 Lu-DOTATATE treatments and 28 131 I-NaI administrations. The median age was 7 years (1-18). The median administered activity of: 131 I-mIBG was 16.2 GBq (6.8-59 GBq) for double infusion patients and 8.1 GBq (5.26-16.25 GBq) for single administrations; 177 Lu-DOTATATE was 7.2 GBq (2.5-7.5 GBq); and 131 I-NaI was 3 GBq for thyroid remnant ablation and 5.5 GBq for cancer therapy. The median number of comforters and carers for all administrations was 2 (range 1-9). The median exposure values for comforters and carers for high-administered activity 131 I-mIBG administrations was 302 µSv (0-5282 µSv); for single fraction 131 I-mIBG 163 µSv (3-3104 µSv); 177 Lu-DOTATATE 6 µSv (1-79 µSv); and 131 I-NaI 37 µSv (0-274 µSv). Only one of the comforters and carers exceeded the dose constraint of 5 mSv. CONCLUSIONS: Doses to comforters and carers were in all but one case within the dose constraint nationally recommended by the Health Protection Agency, now part of Public Health England. New evidence is presented which show that comforter and carer radiation exposure levels from paediatric molecular radiotherapy in routine clinical practice are acceptably low. Pediatr Blood Cancer 2015;62:235-239. © 2014 Wiley Periodicals, Inc.

Paediatric Molecular Radiotherapy: Challenges and Opportunities.

The common contemporary indications for paediatric molecular radiotherapy (pMRT) are differentiated thyroid cancer and neuroblastoma. It may also have value in neuroendocrine cancers, and it is being investigated in clinical trials for other diseases. pMRT is the prototypical biomarker-driven, precision therapy, with a unique mode of delivery and mechanism of action. It is safe and well tolerated, compared with other treatments. However, its full potential has not yet been achieved, and its wider use faces a number of challenges and obstacles. Paradoxically, the success of radioactive iodine as a curative treatment for metastatic thyroid cancer has led to a 'one size fits all' approach and limited academic enquiry into optimisation of the conventional treatment regimen, until very recently. Second, the specialised requirements for the delivery of pMRT are available in only a very limited number of centres. This limited capacity and geographical coverage results in reduced accessibility. With few enthusiastic advocates for this treatment modality, investment in research to improve treatments and broaden indications from both industry and national and charitable research funders has historically been suboptimal. Nonetheless, there is now an increasing interest in the opportunities offered by pMRT. Increased research funding has been allocated, and technical developments that will permit innovative approaches in pMRT are available for exploration. A new portfolio of clinical trials is being assembled. These studies should help to move at least some paediatric treatments from simply palliative use into potentially curative protocols. Therapeutic strategies require modification and optimisation to achieve this. The delivery should be personalised and tailored appropriately, with a comprehensive evaluation of tumour and organ-at-risk dosimetry, in alignment with the external beam model of radiotherapy. This article gives an overview of the current status of pMRT, indicating the barriers to progress and identifying ways in which these may be overcome.

Quantitative SPECT/CT parameters of myocardial 99mTechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake in suspected cardiac transthyretin amyloidosis.

BACKGROUND: 99mTc-labelled bisphosphonates are used for imaging assessment of patients with transthyretin cardiac amyloidosis (ATTR). Present study evaluates whether quantitative SPECT/CT measurement of absolute myocardial 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (Tc-DPD) uptake can diagnose patients with suspected ATTR. METHODS: Twenty-eight patients (25 male, age 80.03 ± 6.99 years) with suspected ATTR referred for Tc-DPD imaging had planar and SPECT/CT imaging of the chest. Three operators independently obtained Tc-DPD myocardial SUVmax and SUVmean above threshold (SMaT) (20, 40 and 60% of SUVmax), using a semi-automated threshold segmentation method. Results were compared to visual grading (0-3) of cardiac uptake. RESULTS: Twenty-two patients (78%) had cardiac uptake (2 grade 1, 15 grade 2, 5 grade 3). SUVmax and SMaT segmentation thresholds enabled separating grades 2/3 from 0/1 with excellent inter- and intra-reader correlation. Cut-off values 6.0, 2.5, 3 and 4 for SUVmax, SMaT20,40,60, respectively, separated between grades 2/3 and 0 /1 with PPV and NPV of 100%. SMaT20,40,60(cardiac)/SUVmean (liver) and SMaT20,40,60(cardiac)/SUVmean(liver/lung) separated grades 2 and 3. CONCLUSION: Quantitative SPECT/CT parameters of cardiac Tc-DPD uptake are robust, enabling separation of patients with grades 2 and 3 cardiac uptake from grades 0 and 1. Larger patient cohorts will determine the incremental value of SPECT/CT quantification for ATTR management.

18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging in HIV-infected patients with lymphadenopathy, with or without fever and/or splenomegaly.

We audited whether 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18FDG PET-CT) imaging could discriminate between different diagnoses in HIV-infected patients presenting with lymphadenopathy, with or without fever and/or splenomegaly. Maximum standardised uptake (SUVmax) values were similar in lymphoma and mycobacterial and fungal infections and were lower but similar in those with human herpesvirus (HHV) 8-associated disease and HIV-associated reactive lymphadenopathy. Nodal 18FDG avidity, with SUVmax ≥10, excluded diagnoses of HHV 8-associated disease and miscellaneous conditions, and HIV-associated reactive lymphadenopathy was additionally excluded in those who had undetectable plasma HIV viral loads. This audit suggests 18FDG PET-CT imaging did not permit discrimination between specific diagnoses but has utility in identifying lymph nodes with increased avidity that could be targeted for biopsy and in ruling out significant pathology.

The absent kidney in 99Tcm-MAG3 renogram: a dramatic reversible consequence of contrast nephrotoxicity superimposed on renal obstruction.

99Tcm-mercaptoacetyltriglycine (MAG3) renogram is a robust imaging technique used to delineate upper urinary tract obstruction. The changes observed on the renogram are often reversible on relief of obstruction. We present two cases illustrating the extreme consequence of contrast nephrotoxicity on pre-existing obstructed kidneys. In one case, this led to severe impairment of perfusion and uptake observed on 99Tcm-MAG3 renogram and in the second case virtual non-visualization of the obstructed kidney. Subsequent treatment of obstruction, led to dramatic improvement in renal function. It is important for clinicians, nuclear medicine physicians and radiologists to be aware of the potential of contrast nephrotoxicity in obstructed kidneys.

Contrast nephrotoxicity and the role of radionuclide renal scan.

Radiographic contrast media-induced nephrotoxicity is an important cause of acute renal failure. The indications of using contrast are usually unavoidable, compelling and continue to expand, especially in the vascular field. When acute renal failure follows such a procedure, it becomes important to establish the presence of contrast nephrotoxicity or an acute occlusive event which may have precipitated the failure. We present two cases of contrast nephrotoxicity in patients with impaired renal function. Radionuclide renal studies with 99mTc-DTPA (Patient 1) and 99mTc-MAG3 (Patient 2), confirmed the presence of acute tubular necrosis and excluded major occlusive vascular events. Renal scintigraphy remains an important but underused test which can rule out obvious renal vascular occlusion and/or support the diagnosis of contrast-related acute tubular necrosis, as the cause of renal failure in these patients.

Validation of renal output efficiency as an objective quantitative parameter in the evaluation of upper urinary tract obstruction.

This is a preliminary study of the parameter, renal output efficiency (ROE), for the quantitation of furosemide (frusemide) response in diuresis renography. This is calculated by a technique independent of variations in uptake rate by the kidneys. Eleven healthy volunteers and 34 patients suspected of upper urinary obstruction were subjected to gamma camera studies using 99mTc-MAG3 and a standard protocol. Furosemide was given at 18 min after the study was started. The ROE was calculated in each kidney and the results were correlated with final diagnosis. The range of ROE in healthy individuals varied between 82% and 98% (mean = 91.6%); while obstructed kidneys showed significantly reduced values (p < 0.001) ranging between 30% and 76% (mean = 56%). In the diagnosis of urinary obstruction, the ROE has a sensitivity of 91%, specificity of 94% and accuracy of 94%. ROE complements conventional diuresis renography and provides better diagnostic yield in patients with impaired renal function.

Clinical evaluation of technetium-99m-L,L-ethylenedicysteine in patients with chronic renal failure.

UNLABELLED: Technetium-99m-L,L-ethylenedicysteine (99mTc-L,L-EC), a new renal radiopharmaceutical, has been shown to have similar excretion characteristics but a higher plasma clearance than 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) in normal volunteers and patients with obstructive nephropathy. This study evaluated 99mTc-L,L-EC in patients with chronic renal failure. METHODS: The clearance of 99mTc-L,L-EC was compared with that of 125l-hippuran in 26 patients with varying degrees of chronic renal impairment (serum creatine 168-1163 mumol/liter). All 26 patients also were imaged with 99mTc-L,L-EC (70-80 MBq). Fifteen patients had further imaging with 99mTc-MAG3 (100 MBq) the following day. RESULTS: A subjective analysis of the 99mTc-L,L-EC images revealed that all were of acceptable quality regardless of creatinine level. In the 15 patients who were imaged with both 99mTc-L,L-EC and 99mTc-MAG3, general image quality and target-to-background ratios were similar. Time-activity curves and mean parenchymal transit times obtained with the two agents were almost identical. Plasma clearance values (mean +/- s.d.) of 99mTc-L,L-EC and 125l-hippuran were 81 +/- 68 ml/min and 114 +/- 104 ml/min, respectively. Mean 99mTc-L,L-EC clearance was 71% of the mean 125l-hippuran value. CONCLUSION: Technetium-99m-L,L-EC provides equally high-quality images to 99mTc-MAG3 in patients with chronic renal failure. Technetium-99m-L,L-EC clearance more closely resembles that of hippuran than does 99mTc-MAG3 clearance. These features together with its ease of preparation make 99mTc-L,L-EC an attractive alternative to 99mTc-MAG3 in patients with chronic renal failure.

Captopril renal scintigraphy in patients with hypertension and chronic renal failure.

UNLABELLED: The aim of this prospective study was to determine the ability of the captopril renogram to reveal the presence of angiotensin II-dependent renovascular disorder in hypertensive patients with chronic renal failure and to assess the possibility of predicting beneficial effect of angiotensin-converting enzyme (ACE) inhibitors on renal function. METHODS: Forty-one patients were evaluated. Baseline renal scintigraphy was performed with 80 MBq of 99mTc-mercaptoacetyltriglycine (MAG3) injected intravenously. Scintigraphy was repeated within a week with 25 mg of oral captopril given 60 min prior to the test. Using the measurements outlined by the Working Party on Diagnostic Criteria of Renovascular Hypertension with Captopril Renography, the patients were categorized into high (7 patients), indeterminate (19 patients) and low (15 patients) probability for renal artery stenosis (RAS). RESULTS: In five of the seven patients with high probability, the presence of RAS was confirmed angiographically and corrective surgical procedure performed in two. In patients with GFR of 10 ml/min/1.73 m2 and/or split renal function of 10% or less, all qualitative and semiquantitative scintigraphic parameters were nonspecific. Mean parenchymal transit time of tracer was a useful parameter to predict the beneficial effect of ACE inhibition therapy in 23 patients (14 low and 9 indeterminate probability of RAS). CONCLUSION: In hypertensive patients with renal failure, captopril renal scintigraphy can be utilized to identify the presence of angiotensin II-dependent renal dysfunction and possibly help to predict the beneficial effect of ACE inhibitor therapy.

Iodine-131-MIBG therapy of a patient with carcinoid liver metastases.

UNLABELLED: Iodine-13I-metaiodobenzylguanidine (MIBG) is highly concentrated by >60% of carcinoid metastases and thus provides a therapeutic opportunity. METHODS: A symptomatic patient with carcinoid liver metastases, unresponsive to chemotherapy combined with interferon-alpha, was subsequently treated with 131I-MIBG. RESULTS: Radionuclide therapy, which was without significant side effects, resulted in symptomatic improvement and reduced urinary 5-hydroxyindoleacetic acid levels. No new metastases were observed for 15 mo after 131I-MIBG therapy. Gross cystic change occurred in existing liver metastases, presumably as a result of ischemic necrosis. Surgical deroofing and aspiration of cysts led to regeneration of normal liver tissue. CONCLUSION: Iodine-131-MIBG therapy can provide prolonged symptomatic relief and improved quality of life in patients with metastatic carcinoid disease unresponsive to other therapies. The antitumor effect of 131I-MIBG was accompanied by few side effects, suggesting that this therapy should be considered in symptomatic patients with an early stage of disease.

Combined rest thallium-201/stress technetium-99m-tetrofosmin SPECT: feasibility and diagnostic accuracy of a 90-minute protocol.

UNLABELLED: Technetium-99m tetrofosmin is a recently developed compound that clears from background organs rapidly. Tetrofosmin has a good correlation with 201Tl. This study assesses the feasibility and diagnostic accuracy of a combined protocol involving rest 201Tl SPECT and stress imaging with 99mTc-tetrofosmin. METHODS: Twenty-five patients (23 men, 2 women; aged 36-73 yr) with known coronary artery disease underwent the combined protocol. Twenty minutes after the resting injection of 201Tl, resting SPECT data were acquired using low-energy, high-resolution collimators. A stress test using adenosine infusion combined with low-level dynamic exercise was performed. The stress data were collected 20 min later. The reconstructed vertical long-axis, horizontal long-axis and short-axis slices were analyzed qualitatively. Analysis was carried out using nine segments of the left ventricle. The segments were reported either as fixed or reversible. The results were compared to coronary angiography results. RESULTS: The sensitivity and specificity for the detection of diseased coronary vessels were 85% and 70% for the left anterior descending territory, respectively, 78% and 71% for the right coronary artery, and 69% and 70% for the left circumflex. Overall, the sensitivity was 80% and the specificity 70%. CONCLUSION: Combined rest 201Tl/stress 99mTc-tetrofosmin SPECT provides a protocol of short duration which displays similar diagnostic accuracy to a protocol using tetrofosmin as a single agent.

Recurrent follicular carcinoma-oxyphilic cell type (Hürthle cell carcinoma) of the thyroid, imaging with iodine-131 and technetium-99m tetrofosmin before and after radiotherapy.

A 68-year-old male with recurrence of malignant follicular carcinoma-oxyphilic cell type of the thyroid after surgery underwent whole body scintigraphy with 131I-sodium iodide and 99Tcm-tetrofosmin (Myoview). 131I scanning demonstrated local uptake most likely to be in the normal remnant, but 99Tcm-Myoview images delineated recurrence of the carcinoma in the neck, with more extensive involvement. We believe that a combination of 131I and 99Tcm-tetrofosmin imaging may be useful to assess the extent of disease in patients with recurrent Hürthle cell type carcinoma of the thyroid.

Rhenium-186 HEDP as a boost to external beam irradiation in osteosarcoma.

In this case report we demonstrate the usefulness of targeted radiotherapy in the form of rhenium-186 HEDP as a method for dose escalation in the treatment of osteosarcoma.

Functional imaging as an aid to decision-making in metastatic paraganglioma.

Malignant paraganglioma is a rare and slow growing tumour of neuroendocrine origin. At the time of diagnosis, the tumour is usually widespread, with limited therapeutic options. A variety of functional imaging studies are available for staging the disease, guiding therapy and monitoring treatment response. These include 123I-MIBG or 131I-MIBG, 111In-pentetreotide or 111In-lanreotide (somatostatin analogues), and 18F-FDG positron emission tomography. Various radionuclides, including 131I and 90Y, can be targeted to the tumour using MIBG or pentetreotide. Such targeted radionuclide therapy may provide valuable long-term palliation in such patients. We present two cases with metastatic paragangliomas who had widespread soft tissue and bone metastases. One patient was treatment naive and the second had received previous chemotherapy. The functional imaging work-up performed and the targeted radionuclide therapies considered in these patients are described. Both patients were treated with 131I-MIBG. Partial tumour response and complete symptomatic and hormonal response was achieved in one patient; in the second patient there was no change.

Sonographic abnormalities of the thyroid gland following radiotherapy in survivors of childhood Hodgkin's disease.

The aims of this study were as follows. (1) To demonstrate the spectrum, frequency and changes on follow-up of sonographic abnormalities in the thyroid gland of survivors of Hodgkin's disease who had received radiotherapy to the neck in childhood. (2) To compare the sonographic findings with clinical examination and radionuclide imaging. (3) To investigate the association between the presence or absence of focal sonographic abnormalities with age at radiotherapy, the interval from radiotherapy, the presence of a raised thyroid stimulating hormone (TSH) and the length of time the TSH had been raised. 46 patients were scanned prospectively and rescanned at 6-18 months. The mean age at first sonography was 22.7 years, the median age at radiotherapy was 12.5 years, and the median interval post-radiation was 10.3 years. Sonographic abnormalities were seen in all 46 patients. 45 had diffuse atrophy and 30 had focal sonographic abnormalities. 18 patients developed new focal sonographic abnormalities on follow-up. Focal sonographic abnormalities were more commonly associated with longer duration of a raised TSH. Two patients had thyroid carcinoma. Sonographic abnormalities of the thyroid are common in patients following neck radiotherapy in childhood. Focal abnormalities are usually associated with a longer duration of raised TSH.

Treatment of neuroendocrine tumours in adults with 131I-MIBG therapy.

This is a retrospective review of 131I-MIBG therapy for metastatic neuroendocrine tumours in 25 adult patients. The tumours comprised 17 carcinoids, six paragangliomas, one somatostatinoma and one intestinal smooth muscle sarcoma. All patients (age range 28-84 years) had stage IV disease and a positive diagnostic 123I-MIBG scan. Patients received 11.1 GBq (300 mCi) of 131I-MIBG given in three cycles at 3-monthly intervals. The mean cumulative dose was 27.7 GBq (751 mCi). Symptomatic response was observed in 80%, hormonal response in 55% and tumour response in 48% (WHO criteria). Of the 25 patients, 40% are still under follow-up. Death was due to disease progression in all except one. The median survival time was 48 months from diagnosis of metastatic disease, and 17 months from the last 131I-MIBG therapy. The 5-year survival rate was 59% (95% confidence interval, 34%-78%). There was no statistical difference in survival between previously treated (chemo/radiotherapy) and treatment-naive patients. Side-effects were minimal and commonly include nausea (in the first 24 h) and a transient fall in platelet count. 131I-MIBG provides a good therapeutic response in patients with metastatic neuro-endocrine tumours.

201Tl myocardial perfusion SPET: adenosine alone or combined with dynamic exercise.

201Tl myocardial perfusion single photon emission tomography (SPET) with pharmacological coronary vasodilatation using adenosine is now often used in the investigation of a patient with ischaemic heart disease (IHD). In this study, we present data from two groups of patients. Group A (n = 40) experienced 201Tl SPET with adenosine only as the pharmacological stress test, using an infusion rate of 140 micrograms kg-1 min-1. Group B patients (n = 50) had the same test combined with low-level dynamic exercise. The side effects were noted for both groups and 201Tl SPET studies were acquired for stress and redistribution images. There was a lesser degree of non-cardiac side effects in patients of group B. There was a significant difference in the haemodynamic parameters between the two groups. There was no significant difference in overall sensitivity (87% versus 90%) and specificity (84% versus 88%) in the detection of IHD between the two groups. In conclusion, addition of low-level dynamic exercise with adenosine is to be preferred to adenosine infusion alone, as this protocol is better tolerated and may enhance the detection of right coronary artery disease (sensitivity = 82% versus 90%, n.s.).

Transmission scanning for attenuation correction of myocardial 201Tl images in obese patients.

For attenuation correction (AC) of 201Tl myocardial perfusion images, an accurate attenuation map is required. This study assessed whether prolonged transmission scanning is required in obese compared to normal-sized patients. Twenty-nine obese patients (mean body mass index 33 kg m-2) underwent sequential emission/transmission imaging for AC using an L-shaped, dual-headed gamma camera fitted with two 153Gd scanning line sources. Transmission data were acquired for 5 s per view (scan time for normal-sized patients) and for 10 s per view and used to reconstruct individual attenuation maps. Emission data were reconstructed using each attenuation map in turn to produce attenuation-corrected images (AC5 and AC10). Tracer distribution in the AC5 and AC10 images was compared by two observers blinded to study type. For each data set, count density was measured in 17 segments of a polar plot and segmental uptake expressed relative to study maximum. Although myocardial count density was low on the 5 s per view transmission images (0.5-13.0 and 3.0-14.0 counts per pixel in the anteroposterior and lateral projections respectively), no significant differences in tracer distribution were seen between the AC5 and AC10 images and these were reported identically. In addition, the mean segmental relative uptake values were similar (P > 0.05) for corresponding segments of the AC5 and AC10 images. We conclude that prolonged transmission scanning is not required in obese compared to normal-sized patients. The transmission scanning protocol used in normal-sized patients is applicable across a wide patient weight range.

99mTc sestamibi scintimammography in the diagnosis of palpable breast masses.

The aim of this prospective study was to evaluate the diagnostic performance of 99mTc sestamibi scintimammography in a region with a low incidence of breast cancer (East, central and West Africa) and to verify the clinical usefulness of this technique in identifying benign breast diseases. Thirty-eight women (age range 22-38 years) with palpable breast masses (n =38) and inconclusive mammograms were included. Prone scintimammography was performed 10 min and 60-90 min in all patients after injection using an isotime acquisition of 10 min. A positive scan for breast cancer was defined as tracer uptake on the 10 min image and retention of activity on the 60-90 min image. A negative scan was defined as uptake on the 10 min image and complete washout of activity on the 60-90 min image. All patients subsequently underwent excisional biopsy of the breast masses and histological confirmation of the pathology. The results of scintimammography and histopathology were in agreement in all patients, revealing 36 benign lesions and two malignant lesions. Histopathologically, the lesions were fibroadenomas (27), fibrocystic disease (five), abscesses (four) and invasive intraductal carcinoma (two). It is concluded that, in regions with high incidence of benign breast diseases in young women, 99mTc sestamibi scintimammography can be used to rapidly characterize benign and malignant breast masses and thereby give priority to the management of those with a serious condition.

Safety of intravenous dipyridamole thallium myocardial perfusion imaging: experience in 435 patients.

Dipyridamole stress 201Tl scintigraphy is widely used in the investigation of myocardial ischaemia. We report our experience of adverse effects observed during this diagnostic procedure. A prospective study was undertaken of 435 consecutive patients (mean age 59 years; 273 males) referred to two nuclear medicine departments for assessment of myocardial perfusion was undertaken. Patients were monitored prior to and following the infusion of dipyridamole. All symptomatic, haemodynamic and electrocardiographic changes were documented. No deaths occurred in this series. Adverse events were observed in 174 (40%) patients. Of these, three patients experienced 'major' adverse events (0.6%) requiring hospitalization (myocardial infarction = 1; chest pain = 1; simple partial seizure = 1). 'Moderate' adverse events occurred in 39 (8.9%) patients and required intravenous aminophylline to reverse effects (ST segment abnormalities = 26; nausea = 7 headache = 3; chest pain = 2; bronchospasm = 1; protracted vomiting = 1; diarrhoea = 1). 'Minor' adverse events were experienced by 132 (30.3%) patients and did not require aminophylline. Sixty per cent of our patients experienced no ill effects from dipyridamole given as an exercise substitute in conjunction with 201Tl imaging. The rest had symptoms which were mostly mild, although a few patients found the experience unpleasant. Only one patient experienced a life-threatening episode.