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.

Role of focal salvage ablative therapy in localised radiorecurrent prostate cancer.

Up to one-third of men can fail radical external beam radiotherapy for primary prostate cancer. Most of these men have expectant management with delayed hormones. However, around half of these men have localised recurrence. Challenges remain in identifying such men accurately, in order to enable them to undergo local salvage therapy which is potentially curative. Currently, this includes radical prostatectomy, brachytherapy and ablative whole-gland therapies, such as cryotherapy and high intensity focused ultrasound, all of which can carry significant morbidity. New approaches may involve targeting the area of recurrence alone--focal salvage therapy--in order to reduce tissue damage and thus reduce morbidity. This requires accurate localisation of intraprostatic recurrent disease and precision targeted ablation.

The role of ¹8fluoro-deoxy glucose combined position emission and computed tomography in the clinical management of anal squamous cell carcinoma.

AIM: Anal squamous cell carcinoma (SCC) is uncommon in the western world but continues to increase in incidence. Optimal treatment and outcome are dependent upon pretreatment staging strategies. We evaluate the role of ¹8fluoro-deoxyglucose (¹8FDG) combined position emission and computed tomography (PETCT) in the management of anal SCC. METHOD: Patients with a histologically confirmed anal SCC underwent standard staging investigations, including computed tomography, Magnetic resonance imaging and examination under anaesthetic. A tumour, node, metastasis (TNM) system was used. All patients subsequently underwent additional whole-body ¹8FDG PETCT scanning. Management was planned accordingly, blinded to ¹8FDG PETCT findings, at a multidisciplinary meeting, and reviewed again following disclosure of PETCT results. RESULTS: Forty patients (24 men), with a median age of 57 years (range 38-87 years), were prospectively recruited. All primary tumours were ¹8FDG avid. PETCT did not alter the T stage but did result in disease upstaging (N and M stages). Management was altered in five (12.5%) patients: one patient was identified to have an isolated distant metastasis, and four patients had ¹8FDG-avid lymph nodes not otherwise detected, all of which were tumour-positive on fine needle aspiration cytology/biopsy. CONCLUSION: PETCT upstages anal SCC and influences subsequent management. PETCT should be considered in the staging of anal SCC, although the definitive benefit of such a strategy requires further evaluation.

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.

FDG-PET in bleomycin-induced pneumonitis following ABVD chemotherapy for Hodgkin's disease--a useful tool for monitoring pulmonary toxicity and disease activity.

Bleomycin-related pneumonitis (BIP) has recently emerged as one of the main causes of death in Hodgkin's disease treated with standard chemotherapy ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). We used 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning in a patient with Hodgkin's disease who developed bleomycin lung toxicity following the 4(th) cycle of chemotherapy. The PET scan done two month after the acute presentation with BIP showed uptake of FDG in the lungs. Following treatment with corticosteroids, the FDG avidity in the lungs disappeared. Corticosteroids were tapered off subsequently, without recurrence of the respiratory symptoms. Conventional CT scanning was not able to distinguish between residual changes and active inflammation. Thus PET represents a useful diagnostic tool and, independently of CT, indicates the resolution of disease activity, even in the presence of residual pulmonary scarring.

Simultaneous 68Ga DOTATATE Positron Emission Tomography/Magnetic Resonance Imaging in Meningioma Target Contouring: Feasibility and Impact Upon Interobserver Variability Versus Positron Emission Tomography/Computed Tomography and Computed Tomography/Magnetic Resonance Imaging.

AIMS: The increasing use of highly conformal radiation techniques to treat meningioma confers a greater need for accurate targeting. Several groups have shown that positron emission tomography/computed tomography (PET/CT) information alters meningioma targets contoured by single observers, but whether this translates into improved accuracy has not been defined. As magnetic resonance imaging (MRI) is the cornerstone of meningioma target contouring, simultaneous PET/MRI may be superior to PET/CT. We assessed whether 68Ga DOTATATE PET imaging (from PET/CT and PET/MRI) reduced interobserver variability (IOV) in meningioma target volume contouring. MATERIALS AND METHODS: Ten patients with meningioma underwent simultaneous 68Ga DOTATATE PET/MRI followed by PET/CT. They were selected as it was anticipated that target volume definition in their cases would be particularly challenging. Three radiation oncologists contoured target volumes according to an agreed protocol: gross tumour volume (GTV) and clinical target volume (CTV) on CT/MRI alone, CT/MRI+PET(CT) and CT/MRI+PET(MRI). GTV/CTV Kouwenhoven conformity levels (KCL), regions of contour variation and qualitative differences between PET(CT) and PET(MRI) were evaluated. RESULTS: There was substantial IOV in contouring. GTV mean KCL: CT/MRI 0.34, CT/MRI+PET(CT) 0.38, CT/MRI+PET(MRI) 0.39 (P = 0.06). CTV mean KCL: CT/MRI 0.31, CT/MRI+PET(CT) 0.35, CT/MRI+PET(MRI) 0.35 (P = 0.04 for all groups; P > 0.05 for individual pairs). One observer consistently contoured largest and one smallest. Observers rarely decreased volumes in relation to PET. Most IOV occurred in bone followed by dural tail, postoperative bed and venous sinuses. Tumour edges were qualitatively clearer on PET(MRI) versus PET(CT), but this did not affect contouring. CONCLUSION: IOV in contouring challenging meningioma cases was large and only slightly improved with the addition of 68Ga DOTATATE PET. Simultaneous PET/MRI for meningioma contouring is feasible, but did not improve IOV versus PET/CT. Whether volumes can be safely reduced according to PET requires evaluation.

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.

Defining the target in cancer of the oesophagus: direct radiotherapy planning with fluorodeoxyglucose positron emission tomography-computed tomography.

AIMS: Target definition in radiotherapy treatment planning (RTP) of oesophageal cancer is challenging and guided by a combination of diagnostic modalities. This planning study aimed to evaluate the contribution of single positron emission tomography-computed tomography (PET-CT) in the treatment position to RTP. MATERIALS AND METHODS: Nineteen patients referred for radiotherapy from April to December 2008 were retrospectively identified. Two sets of target volumes were delineated using the planning CT and the (18)F-fluoro-deoxy-D-glucose ((18)F-FDG) PET-CT data sets, respectively. Target volumes were compared in length, volume and geographic conformality. Radiotherapy plans were generated and compared for both data sets. RESULTS: PET-CT planning target volume (PET-CT(PTV)) was larger than the CT target (CT(PTV)) in 12 cases and smaller in seven. The median PTV conformality index was 0.82 (range 0.44-0.98). Radiotherapy plans conforming to normal tissue dose constraints were achieved for both sets of PTV in 16 patients (three patients could not be treated to the prescription dose with either technique due to very large target volumes and significant risk of normal tissue toxicity). Previously undetected locoregional nodal involvement seen on PET-CT in three cases was localised and included in the PTV. In nine cases, the CTPTV plan delivered less than 95% dose to 95% of the PET-CT(PTV), raising concern about potential for geographical miss. CONCLUSION: A single scan with diagnostic PET-CT in the treatment position for RTP allows greater confidence in anatomical localisation and interpretation of biological information. The use of PET-CT may result in larger PTV volumes in selected cases, but did not exclude patients from radical treatment within accepted normal tissue tolerance.

A comparison of the psychological burden of PET/MRI and PET/CT scans and association to initial state anxiety and previous imaging experiences.

OBJECTIVE: To investigate the level of psychological burden experienced by patients undergoing positron emission tomography (PET)/MRI scanning compared with PET/CT. METHODS: 100 adult patients referred for PET/CT and underwent PET/MRI scanning were eligible. Initial state, psychological burden of PET/CT and PET/MRI, scan satisfaction and preference were assessed using a purpose-designed questionnaire, comprising 61 five-point Likert scale questions and a three-point tick box question indicating preference between PET/CT and PET/MRI. State anxiety was assessed using the state portion of the State Trait Anxiety Inventory. Wilcoxon signed-rank tests compared psychological burden experienced by participants following PET/CT and PET/MRI scan. RESULTS: A greater level of psychological burden was experienced by patients during PET/MRI than PET/CT p ≤ 0.001, consistent with patients' preference for PET/CT over PET/MRI (p = 0.013). There was a significant relationship between PET/CT psychological burden and initial state (r = 0.386, p ≤ 0.001). No significant relationship was identified between Initial state and psychological burden of PET MRI (r = -0.089; p = 217). There was a significant relationship between psychological burden of PET/CT and PET/MRI (r = 0.354; p = 0.001). CONCLUSION: Patients' experience increased psychological burden during PET/MRI compared with PET/CT. Previous scanning experiences and patients' interactions prior to and during PET/MRI improved patient satisfaction. Interventions could be implemented to improve imaging outcome. ADVANCES IN KNOWLEDGE: This study provides evidence for the increased psychological burden of PET/MRI compared with PET/CT, and that people prefer the PET/CT procedure. We have shown that the patients who expressed a preference for PET/MRI demonstrated significantly lower psychological burden for that procedure than those that preferred PET/CT, which indicates that the benefit of reduced psychological burden could be facilitated by an appropriate intervention.

The FORECAST study - Focal recurrent assessment and salvage treatment for radiorecurrent prostate cancer.

BACKGROUND: One-third of men may experience biochemical failure by 8years following radical radiotherapy for localised prostate cancer. Over 90% of men are started on androgen deprivation therapy (ADT) which is non-curative and confers systemic side-effects. Focal salvage therapy (FST) limits collateral tissue damage and may improve therapeutic ratios. In order to deliver FST, distant disease must be ruled-out and intra-prostatic disease must be accurately detected, localised and characterised. AIM: FORECAST - Focal Recurrent Assessment and Salvage Treatment - is a study designed to evaluate a novel imaging-based diagnostic and therapeutic complex intervention pathway for men who fail radiotherapy. METHODS: Men with biochemical failure following radical prostate radiotherapy, prior to salvage therapy will be recruited. They will undergo whole-body multi-parametric MRI (WB-MRI), choline PET/CT, bone-scan and pelvic-mpMRI and then MRI transperineal-targeted biopsies (MRI-TB) and Transperineal Template Prostate Mapping Biopsy (TPM). Those suitable for FST will undergo either high intensity focused ultrasound (HIFU) or cryotherapy. RESULTS: Primary outcome measures: a) the accuracy of WB-MRI to detect distant metastatic disease; b) accuracy of prostate mpMRI in local detection of radiorecurrent prostate cancer; c) detection accuracy of MRI-TB; and d) rate of urinary incontinence following FST. CONCLUSION: Focal salvage therapy may confer lower rates of morbidity whilst retaining disease control. In order to deliver FST, intra- and extra-prostatic disease must be detected early and localised accurately. Novel diagnostic techniques including WB-MRI and MRI-TB may improve the detection of distant and local disease whilst reducing healthcare burdens compared with current imaging and biopsy strategies.

Technetium-99m-MDP patterns in patients with painful shoulder lesions.

UNLABELLED: There is no consensus on the optimum mode of imaging in patients with painful shoulder lesions. There is a particular paucity of scintigraphic data. As a result, the strengths and weaknesses of scintigraphy cannot be adequately compared to other imaging techniques used in shoulder imaging. This study evaluated whether specific patterns of scintigraphic abnormality could be detected in patients with painful shoulders seen in rheumatological practice using 99mTc-methylene diphosphonate (MDP). METHODS: Scintigraphic abnormalities were recorded in consecutive patients presenting to a rheumatology clinic with unilateral shoulder pain. Patients were subdivided according to patterns of clinical abnormality consistent with a working diagnosis of a lesion located in the subacromial region, adhesive capsulitis (frozen shoulder) or a lesion likely to be located in the glenohumeral joint. Patterns of radiopharmaceutical distribution in different regions of the shoulder were evaluated in the light of clinical data and the results of shoulder radiographs. RESULTS: Technetium-99m-MDP scans were abnormal in 19 of 24 (79%) patients, and radiographs were abnormal in 8 of 24 (33%) patients. Distinct patterns of 99mTc-MDP image abnormality were identified: an increase in 99mTc-MDP uptake in the coracoid, acromion and medial humeral head on anterior planar images, together with an absence of posterior planar image abnormality, frequently occurred in association with a working diagnosis of a lesion located in the subacromial region. Posterior planar 99mTc-MDP image abnormalities always occurred in patients with clinical features consistent with a diagnosis of adhesive capsulitis. There was an 85% agreement between two observers' scores when 99mTc-MDP distribution in specific shoulder regions was graded. CONCLUSION: Distinct patterns of 99mTc-MDP distribution may be associated with clinically-distinct patterns of abnormality in patients with painful shoulder lesions. Further studies to elucidate a role for 99mTc-MDP scintigraphy in this patient group are warranted.

Imaging of carcinoid tumors with iodine-123 metaiodobenzylguanidine.

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.

Pachydermoperiostosis: technetium-99m-methylene diphosphonate scintigraphic pattern.

We present two cases of pachydermoperiostosis. Both patients presented with joint pains and swelling. Bone scan revealed marked pericortical uptake involving the distal end of long bones. The distribution pattern and differential diagnosis of the scan abnormalities are discussed.

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.

Ocular radioimmunoscintigraphy: sensitivity and practical considerations.

Ocular radioimmunoscintigraphy was performed in 20 patients using 99mTc-labeled monoclonal antibody 225.28S, F(ab')2 fragments. Radioimmunoscintigraphy was positive in 13 patients and the diagnosis of ocular melanoma was confirmed by enucleation of the eye or clinical follow-up. Scintigraphy was positive in one patient with lymph node metastasis from an ocular melanoma. In six patients immunoscintigraphy was negative. Using this technique a sensitivity of 92.8% was achieved for detecting ocular melanomas. Single photon emission tomography helped to separate the lesions situated in the nasal quadrant of the eye from the adjacent nasopharyngeal activity. With appropriate imaging techniques small tumors of the order of 3 x 5 x 3 mm could be detected clearly.

A scintigraphic comparison of iodine-123-metaiodobenzylguanidine and an iodine-labeled somatostatin analog (Tyr-3-octreotide) in metastatic carcinoid tumors.

A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We compared an 123I-labeled somatostatin analog Tyr-3-octreotide (TOCT) and 123I-labeled metaiodobenzylguanidine (MIBG) scintigraphy in seven patients with histologically proven metastatic carcinoid tumors. The optimum time for identifying tumor uptake on scanning after [123I]MIBG was 24-48 hr, and after 123I-TOCT 10-30 min postinjection. Both radiopharmaceuticals showed a varying spectrum of tracer uptake ([123I]MIBG showed no uptake in one patient; minimal in two; moderate in two; and intense in two; 123I-TOCT showed no uptake in two patients; minimal uptake in one; moderate uptake in two; and intense uptake in two). In two patients, 123I-TOCT identified metastatic lesions not seen by [123I]MIBG scintigraphy. These preliminary results suggest that [123I]MIBG and 123I-TOCT are useful and complementary imaging techniques for detecting metastatic carcinoid tumors.