A new pharmacokinetic model for 90Y-ibritumomab tiuxetan based on 3-dimensional dosimetry.

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of 90Y-Ibritumomab tiuxetan (90Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with 90Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of 111In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.

[Usefulness of nuclear medicine in Erdheim-Chester disease: A Lille experience]. / Intérêt de la médecine nucléaire dans la maladie d'Erdheim-Chester : une expérience lilloise.

INTRODUCTION: Erdheim-Chester disease is a rare form of non-langerhans histiocytosis and its etiology is still not well established. The aims of the study were to assess the value of the bone scintigraphy and the 18F-FDG PET/CT for the diagnostic and for the latter in the therapeutic evaluation. METHODS: We retrospectively reviewed 49 patients suspected of Erdheim-Chester disease between 2004 and 2016. Bone scintigraphy was compared with histopathology and PET-CT to conventional morphological examinations and bone scintigraphy. For therapeutic evaluation, thresholds similar to PERCIST 1.0 were used. RESULTS: Forty-nine bone scintigraphy were evaluated with a sensitivity of 100%, a specificity 97%, a positive predictive value 90% and a negative predictive value of 100%. Eight patients had at least an initial PET-CT. The sensitivity compared to conventional morphological examinations differed from the location but was excellent for orbital, bone and vascular involvements. Specificity was comparable between the different examinations. Six patients treated with interferon® and three with vemurafenib® were followed by PET-CT. PET-CT, in agreement to clinicobiological data, identified 4 partial responses and one complete response with interferon® et two partial responses and one complete response with vemurafenib®. CONCLUSION: Our retrospective study suggests that bone scintigraphy and 18F-FDG PET/CT could be useful in the initial assessment of Erdheim-Chester disease but also for the latter in the therapeutic evaluation.

Long term use of metformin in idiopathic cyclic edema, report of thirteen cases and review of the literature.

INTRODUCTION: Idiopathic cyclic edema (ICE) is a rare cause of edema. To date, there is no standard of care. The physiopathology of ICE could be explained by an impairment of capillary permeability. In 1995, a study demonstrated the efficacy of metformin on symptoms and capillary permeability. We evaluated ICE-patients who were treated with metformin in our department. METHODS: We retrospectively included patients diagnosed for ICE between January 1997 and October 2013. ICE was diagnosed in the presence of edema after excluding other etiologies. LANDIS test was used to support ICE diagnosis in all patients. The absence of edema at follow-up was considered as complete response (CR), partial decreased was considered as partial response (PR). Adverse events were recorded. RESULTS: Thirteen patients have accepted to use metformin. The median treatment duration was 28.5 months [8-167] and the median follow-up of treated patients was 40.5 months [14-167]. CR was reached in 10 patients (77%), and PR in 2 patients (15%). Two patients reported side-effects as diarrheas and one of them stopped the treatment due to mild diarrhea. CONCLUSION: We report the interest and tolerance of the long-term use of metformin in ICE. No severe adverse events were noticed. A prospective study is needed to confirm the efficacy of metformin in ICE-patients.

Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.

Comparisons of dosimetric approaches for fractionated radioimmunotherapy of non-Hodgkin lymphoma.

AIM: The aim of this study was to compare different dosimetric approaches on therapy naïve patients enrolled in a multicentre fractionated radioimmunotherapy trial, to determine which methodological approach correlates with bone marrow toxicity. METHODS: Twenty-height non-Hodgkin lymphoma patients were treated with one or two fractions of 90Y-Ibritumomab-Tiuxetan (11.1 MBq/kg) 8 to 12 weeks apart in four different institutions. Quantitative imaging with 111In-Ibritumomab-Tiuxetan (185 MBq) was performed at 0, 1, 4 and 7 days after infusion, starting two weeks before the therapeutic administration. A whole-body (WB) CT scan was also acquired prior to the 111In-Ibritumomab injection, for attenuation correction purposes and was segmented to derive patient-specific organ masses. All dosimetry processing was centralized in a single institution. The first method (M_2D) was based on geometric mean WB scans, corrected for attenuation, scatter and organs superposition. The second method (M_2.5D) was based on the computed assisted matrix inversion approach and used segmented CT scans. The third method (M_3D) used iterative reconstruction of tomographic scans, corrected for attenuation, scatter and collimator response. Absorbed doses were estimated for lungs, liver, kidneys and spleen using MIRD S values adjusted for organ masses. Bone marrow (BM) absorbed doses were evaluated according to imaging methods (3) and compared to blood-based approaches. RESULTS: For some patients, organ masses such as liver or spleen significantly differed from male/female reference masses, whereas lungs and kidneys masses were relatively constant. Except for lungs, absorbed doses estimated by M_2D were higher than those from M_2.5D and these, in turn, were higher that those calculated from M_3D (Wilcoxon P<8.6e-4). Median organ absorbed dose estimates were equivalent for both fractions except for the spleen. In fact, spleen absorbed doses for the second fraction were lower than those for the first fraction, regardless of the approach. Possible explanations are that patient spleen masses were kept constant for analysis of both fractions and/or that spleen uptake was lowered after the first fraction. Estimation of BM absorbed doses from blood sampling was unable to predict platelet toxicity, but image-based methods performed better. Additionally, for most organs, the absorbed dose delivered by the first fraction could predict that delivered by the second fraction. CONCLUSION: These results confirm that different acquisition/processing protocols will lead to statistically different absorbed doses. Additionally, image-based dosimetric approaches are needed in order to correlate absorbed dose to bone marrow toxicity.

FDG-PET in the assessment of patients with follicular lymphoma treated by ibritumomab tiuxetan Y 90: multicentric study.

BACKGROUND: The aim of this study is the 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) evaluation following radioimmunotherapy (RIT) with ibritumomab tiuxetan Y 90 in patients with non-Hodgkin's follicular lymphoma (FL). MATERIALS AND METHODS: We retrospectively analyzed data from 59 relapsed or refractory FL patients treated with ibritumomab tiuxetan Y 90 in four different PET centers who had a PET scan carried out before and after RIT. Possible predictive factors of progression-free survival (PFS) were studied through univariate and multivariate analysis. RESULTS: The post-RIT PET documented 45.8% complete responders (CR), 25.4% partial responders (PR) and 28.8% nonresponders [stable disease + progressive disease], with an overall survival of 71.2% (range 59.5%-90.9%). With a median follow-up period of 23 months, the univariate analysis documented a statistically significant relation between disease extent before RIT and response to treatment with respect to PFS (P = 0.015), while all the other prognostic factors showed no significant correlation. When carrying out the multivariate analysis, post-RIT PET resulted as the lonely independent predictor of PFS (P < 0.00001). CONCLUSIONS: RIT is an effective therapy in FL patients, as confirmed in our study too. Disease extension before treatment and response to RIT, as assessed by FDG-PET, result as main predictors of PFS, with the post-RIT PET result being the only independent predictive factor.

An easy-to-use phantom and protocol for weekly PET quality assessment: a multicenter study.

The authors have developed a simple phantom and dedicated software for the quality assessment of positron emission tomography (PET) scanners. The phantom is a parallelepiped box filled with a relatively low activity 18FDG solution and in which simple test objects are placed. Various image quality parameters are checked, including signal-to-noise ratio, image uniformity, slice thickness, slice sensitivity profile, spatial resolution, and dose calibration accuracy. Automatic image analysis consists in detecting surfaces and objects, defining regions of interest, acquiring reference point coordinates, and establishing gray-scale profiles. The total time needed for quality assessment (preparation and image acquisition) is less than 15 min with 37 MBq (1 mCi) 18FDG. The system's ease of use encourages frequent image quality assessment-for example, the comparison of PET scanners in interdepartment studies and the monitoring and evaluation of possible drifts over time. By way of an example, the authors present weekly quality assessment results obtained over up to 7 months at four PET facilities.

A new method based on both fuzzy set and possibility theories for tumor volume segmentation on PET images.

A new automatic method for tumor volume segmentation on PET images has been developed. The method introduced in this paper is based on previous works in MRA segmentation and involves both fuzzy set and possibility theories. Visual results prove the method efficiency which is confirmed by obtained Jaccard index.

[Positron emission tomography: current use in internal medicine and future perspectives]. / La tomographie d'émission de positons en médecine interne: applications actuelles et perspectives d'avenir.

PURPOSE: Fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising imaging technique that has already proven effective in modifying patient care in oncology. Fluorodeoxyglucose still remains the main radiopharmaceutical agent routinely used for PET imaging. A growing interest has recently lead to broaden PET research on benign disorders. The field of inflammatory or immune diseases and globally the field of internal medicine could also be impacted by FDG-PET. MAIN POINTS: Great vessels vasculitides and fever of unknown origin have both been studied by several teams and could become indications for PET. In addition, current indications now extend to paraneoplastic syndromes. It is thus possible to foresee that the clinical applications for PET will continue to expand in these patients. PERSPECTIVES AND PROJECTS: In the future, inflammatory arthritis, chronic inflammatory bowel diseases, systemic erythematous lupus, histiocytosis, or pulmonary and retroperitoneal fibrosis might benefit from PET even if, available data remains scarce to this day. Although PET will probably alter the landscape of patient management in internal medicine in the near future, additional clinical research is still needed to ascertain the exact role of PET.

[18FDG PET: a new criterion for disease activity in Takayasu arteritis]. / La TEP au 18FDG au cours de l'artérite de Takayasu: un marqueur d'activité de la maladie.

INTRODUCTION: Takayasu arteritis (TA) is an inflammatory arteritis affecting large vessels, predominantly the aorta, its main branches, and the pulmonary arteries. Up to now, arteriography was considered as the "gold standard". But others exams are emerging in the management of TA: vascular ultrasound, angio-scanner, magnetic resonance imaging and 18FDG positron emission tomography (18FDG PET). Such investigations allow a study of the lumen but also of the arterial walls. However, at the time, no biological or radiological test is able to determine the activity of TA. 18FDG PET could be effective to estimate the disease activity. EXEGESIS: We report the case of a young woman for who 18FDG PET permit to assert a relapse of TA. CONCLUSION: 18FDG PET could be effective to estimate the disease activity.

[Are preoperative examinations useful in the management of patients with renal hyperparathyroidism?]. / L'imagerie préopératoire des hyperparathyroïdies des insuffisants rénaux a-t-elle un intérêt en pratique clinique?

AIM OF THE STUDY: To evaluate the efficiency of preoperative parathyroid ultrasonography and scintigraphy in the management of renal hyperparathyroidism. PATIENTS AND METHODS: The charts of the last consecutive 200 patients who underwent surgery for renal hyperparathyroidism from 1998 to 2003 were retrospectively reviewed to collect data concerning parathyroid gland function, results of preoperative ultrasonography and scintigraphy, as well as modalities and results of surgical exploration. RESULTS: Ultrasonography and scintigraphy sensibilities were 36.4% and 49.3%, respectively. Efficiency of both examinations was improved when they were combined (sensibility of 64.7%) and in those patients managed for recurrent hyperparathyroidism. Were more often detected by preoperative examinations glands with high weight and/or greatest diameter, orthotopic and inferior glands as well as glands exhibiting nodular hyperplasia content upon pathological examination. CONCLUSION: Parathyroid ultrasonography and scintigraphy are of poor interest in the management of renal hyperparathyroidism. In a preoperative setting, they should be performed only in patients with recurrent disease.

Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of osteomyelitis in the diabetic foot.

OBJECTIVES: The diagnosis of osteomyelitis in patients with diabetic foot is difficult both clinically and radiologically. An early diagnosis is crucial to optimize therapeutic strategy. Among the diagnostic methods currently used, scintigraphy with ex-vivo labelled white blood cells is the gold standard, but cannot be performed in all centers; therefore 67Gallium citrate (67Ga) imaging in combination with a bone scintigraphy is still widely used. METHOD: The results of imaging 24 diabetic patients with 31 suspected osteomyelitic lesions using the antigranulocyte Fab' fragment (Sulesomab or LeukoScan or immunoscintigraphy) were prospectively compared with results from the bone scan coupled with 67Ga. The diagnosis of osteomyelitis was confirmed by either biopsy or follow-up, radiological imaging and clinical outcome. RESULTS AND CONCLUSION: Sulesomab correctly identified 12 of 18 osteomyelitic lesions while 67Ga was able to detect only 8 of 18. Therefore the sensitivity is 67% for Sulesomab and 44% for 67Ga. Among the 13 non-osteomyelitic lesions imaging with Sulesomab was able to rule out infection in 11 cases and 67Ga in 10 cases. The specificity is therefore 85% for Sulesomab and 77% for 67Ga. Image interpretation for Sulesomab in this group of patients is occasionally suboptimal when imaging is performed at 3 hours post injection. High vascular background in the early images may obscure infection especially in small bones. Practically, scintigraphy with Sulesomab is fast and simple due to ease of labeling, no ex-vivo handling of blood, low radiation and provides rapid diagnosis. The diagnosis of osteomyelitis obtained by the antibody fragment scintigraphy influences the management (guided biopsy) and therapy. In several patients, imaging with Sulesomab was able to rule out osteomyelitis, helping to avoid useless antibiotic therapy and its associated side effects.

[Paragangliomas: clinical and secretory profile. Result of 39 cases]. / Paragangliomes: profil clinique et sécrétoire. A propos de 39 cas.

THIS RETROSPECTIVE STUDY AIMS: To define a clinical and secretory profile of paragangliomas extra-adrenal chromaffin tumors. METHODS: From 1971 throughout 2002, 39 paragangliomas have been observed in 38 patients (22 male, 16 female, average age 41,2 years). RESULTS: Four were located above the diaphragm, 35 were sub-phrenic (6 of the organ of Zuckerkandl), 32 secreted catecholamines, 23 were hypertensive (with only one without hypersecretion of catecholamines). Among 29 (131)I-metaiodobenzylguanidine scans (MIBG) reviewed, 20 tumors took up the radiopharmaceutical. The treatment was surgical in 35 cases with addition of external radiotherapy and MIBG in one case each; two patients died before any treatment. Two patients with persistent disease after surgery were successfully treated by surgery or MIBG. Histologically, 20 were malignant and 17 were seemingly benign. All exclusive dopamine secreting paragangliomas were malignant. Six patients relapsed two of which for a tumor initially classified as benign. The treatment of recurrences was surgical, by MIBG or by external radiotherapy. Nine patients had a family history of chromaffin tumor(s). The genetic survey made in five of these nine patients was positive in all cases.

Prospective evaluation of the impact of [18F]fluoro-2-deoxy-D-glucose positron emission tomography of resectable colorectal liver metastases.

BACKGROUND: The aim of this study was to assess the additional value of information provided by positron emission tomography (PET) with [(18)F]fluoro-2-deoxy-D-glucose (FDG) over that provided by computed tomography (CT) in patients with resectable liver metastases from colorectal cancer. METHODS: Between October 2001 and November 2002, a prospective double-blind comparison of preoperative FDG-PET and thoracoabdominal CT was performed in 53 patients with potentially resectable liver metastases from colorectal cancer. All resected metastases were subjected to histological examination. RESULTS: Histological examination confirmed the presence of malignant or benign lesions detected by PET and/or CT in 95 per cent of instances. Overall sensitivity (78 per cent) and accuracy (88 per cent) of PET were equivalent to those of CT (76 and 86 per cent respectively). The sensitivity of PET was equivalent to that of CT for hepatic sites (both 79 per cent), but was superior for extrahepatic abdominal sites (63 and 25 per cent respectively). PET provided additional information in five patients, mainly by revealing abdominal extrahepatic metastases, but falsely upstaged three patients. CONCLUSION: Whole-body FDG-PET may identify unrecognized extrahepatic metastases in patients with potentially resectable liver metastases imaged by CT. However, additional information provided by PET is not as reliable as suggested by earlier retrospective studies.

[Reoperation for persistent or recurrent primary hyperparathyroidism. Seventy-seven cases among 1888 operated patients]. / Réinterventions pour hyperparathyroïdisme primaire persistant ou récidivant. Soixante-dix-sept cas sur 1888 opérés.

AIMS: To analyse the results of re-operations for persistent (p) or recurrent (r) primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: From 1965 throughout 2001, 1888 patients were operated on for PHPT. The cure rate after initial surgery was 97.6%. Seventy-seven (4.1%) were reoperated for p PHPT (n = 54) or r PHPT (n = 23). Thirty-two out of 77 (41%) had been primarily operated elsewhere. In 15 cases (20%) PHPT was genetically determined. The re-operation was undertaken on average 40.7 months after initial surgery (1 day-190 months). RESULTS: Two out of 77 were cases of familial hypocalciuric hypercalcaemia. Among the 75 patients reoperated for true PHPT, 23 (31%) had uniglandular disease (UGD) and 52 (69%) had multiglandular disease (MGD). There were two cases of recurrent parathyroid carcinoma. Overall 97 pathological glands were resected, 37% being orthotopic and 63% heterotopic. The re-operation was performed by a cervical approach in 80%, by a mediastinal approach in 15%, whereas 5% involved excision of antebrachial implants. In 96% of cases the parathyroid glands were in the cervical position. Among the preoperative localisations studies the sensitivity of scintigraphy utilising 2-methoxyisobutyl-isonitril (MIBI) was 61%. Utilising both MIBI and cervical ultrasound the sensitivity was 64%. Sixty-eight out of 75 (91%) were cured of their hypercalcaemia, but at the cost of permanent hypoparathyroidism in 9% of cases. No sporadic adenoma appears to have been missed. The seven failures after re-operation (9%) involved five cases of MGD, of which four were sporadic, two cases of carcinoma and one case of parathyreomatosis. 39 patients (51%) had more than four parathyroid glands and in 22/39 cases at least one supernumerary gland was pathological. CONCLUSION: The re-operations for PHPT were essentially due to MGD that was either sporadic or genetically determined. Often the offending supernumerary gland was not detected by imaging studies. Avoiding failures entails an initial bilateral cervicotomy with thymic exploration after MIBI scintigraphy to exclude a mediastinal focus.

[Utilization of PET scan in breast and gynaecologic cancers]. / Apport de la tomographie d'émission de positons au [18F]-fluoro-désoxy-glucose en cancérologie gynécologique et mammaire.

The use of fluorine-18 fluorodeoxyglucose (FDG) in positron emission tomography (PET) is a major advance in imaging in the recent past. Its use in breast and gynaecologic cancers is not well established and needs to be discussed for each patient. This discussion must rely on a better knowledge of potential interests as well as of the limits of metabolic or logistic limits of PET.

[Radioguided surgery for primary hyperparathyroidism: 100 cases]. / Chirurgie radioguidée de l'hyperparathyroïdisme primaire.

One hundred patients with primary hyperparathyroidism underwent radioguided surgery within 90 to 180 minutes following IV injection of a diagnostic dose of MIBI and after parathyroid scanning with planar and oblique views. Exclusion criteria were thyroid pathology requiring surgery and suspicion of multiple endocrine neoplasia. A>20% step-up between the background noise and tissue uptake was the diagnostic threshold for parathyroid hyperfunctionning tissue, and this was observed in only 15% of cases overall all cured, but two. This method of detection is technically demanding and various angles of application of the probe can result in significant discrepancies of recorded uptake for the same spot. Our results demonstrate a physiological step-up between the ipsilateral unaffected upper and lower quadrants of the neck (range: - 34% to - 5%), seemingly because of the proximity of supra-aortic vessels (upper neck-upper mediastinal gradient: - 57% to - 21%). Therefore, significant ratios are meaningful only between either the symmetrical left and right controlateral quadrants, 8% of pre-operative scannings were non-contributory, and probe detection was contributory in 3/8 cases only. Benefit of the technique is limited in routine, but it can be helpful in redo cases if the offending gland is not located in close surroundings of tissues physiologically taking up the radio pharmaceutical (salivary glands, great vessels and heart).

Simultaneous determination of pulmonary and intestinal permeability in patients with alcoholic liver cirrhosis.

The aim of this prospective study was to assess pulmonary and intestinal permeability (PP and IP, respectively) in patients with alcoholic liver cirrhosis (ALC). Thirty-five non-smoking patients with biopsy-proven ALC were included (mean grade B in Child's classification). None had a previous history of pulmonary disease and all had a normal chest radiograph and computed tomography scan. Lung function tests and bronchoalveolar lavage (BAL) were also performed. The PP was studied by measuring the lung to blood clearance of inhaled 99mTc-DTPA aerosol. Clearance half-time (T 1/2, in minutes) and residual activity (RA in %) were obtained from exponential fitting of the right pulmonary clearance curve. IP was concurrently evaluated by measuring the urinary recovery of ingested 51Cr-EDTA, according to Bjarnason's technique and expressed as a percentage of the total oral dose. Results were compared with those obtained in non-smoking healthy control subjects. PP was significantly (P<0.05) increased in patients with ALC (T 1/2 65.9 +/- 32.2 min, RA 87.1% +/- 6.7%) versus control subjects (T 1/2 85.2 +/- 20.8 min, RA 92.8% +/- 2.6%). IP was not significantly different between patients and controls (2.39% +/- 2.20% vs 1.74% +/- 0.81%). A significant correlation (P<0.05) was found between PP and total cell number in BAL and total lymphocyte number in BAL. In conclusion, in patients with ALC, PP is increased without any association with IP, the severity of cirrhosis according to Child's classification or the results of pulmonary function tests. These findings may reflect primary involvement of the alveolar epithelium. In patients with ALC, PP is correlated with total cell number and total lymphocyte number. Increased PP may be due to activated cytotoxic lymphocytes and/or abnormal macrophage activity.

[Radioguided surgery for primary hyperparathyroidism. Experience in 75 cases]. / Chirurgie radioguidée de l'hyperparathyroïdie primaire. Expérience de 75 observations.

STUDY AIM: To report feasibility and efficacy of radioguided mini invasive hyperparathyroidism surgery. PATIENTS AND METHOD: From November 1998 to August 2000, 75 patients with primary hyperparathyroidism have been operated on by radioguided surgery within 90 to 180 minutes following i.v. injection of a diagnostic dose of MIBI and after parathyroid scanning with planar and oblique views. Exclusion criteria were thyroid pathology requiring surgery and suspicion of multiple endocrine neoplasia. A 20% step-up between the background noise and tissue uptake was the diagnostic threshold for parathyroid hyperfunctioning tissue. RESULTS: A 20% step-up was observed in only 17% of cases overall; all cured, but two. Various angles of application of the probe can result in significant discrepancies of recorded uptake for the same spot. These results demonstrate a physiological step-up between the ipsilateral unaffected upper and lower quadrants of the neck (range: -17 to -8%), because of the proximity of supraortic vessels (upper neck-upper mediastinal gradient: -44 to -30%). Therefore, significant ratios are meaningful only between either the symmetrical left and right controlateral quadrants respectively, and not between the upper and the lower ipsilateral quadrants. Eleven per cent (8/75) of preoperative scannings were non-contributory, and probe detection was contributory in 3/8 cases only. CONCLUSION: Benefit of the technique is limited in routine, but it can be helpful in redo cases if the offending gland is not located in close surroundings of tissues physiologically taking up the radiopharmaceutical (salivary glands, great vessels and heart).