Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Clinical value of negative 68Ga-PSMA PET/CT in the management of biochemical recurrent prostate cancer patients.

PURPOSE: To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR). METHODS: One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables. RESULTS: In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1-20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9-70.4) whereas the 24-month CRFS was 34.8% (range, 24-45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35-5.57] for subset 3 versus subset 1; HR of 2.08 [1.11-3.88] for subset 2 versus subset 1). CONCLUSION: 68Ga-PSMA PET/CT negativity in early BCR patients (PSA < 0.5 ng/mL) with low-grade primary prostate cancer (ISUP1 and 2) may support the exploration of a clinical surveillance approach in future prospective studies.

Stellar populations dominated by massive stars in dusty starburst galaxies across cosmic time.

All measurements of cosmic star formation must assume an initial distribution of stellar masses-the stellar initial mass function-in order to extrapolate from the star-formation rate measured for typically rare, massive stars (of more than eight solar masses) to the total star-formation rate across the full stellar mass spectrum 1 . The shape of the stellar initial mass function in various galaxy populations underpins our understanding of the formation and evolution of galaxies across cosmic time 2 . Classical determinations of the stellar initial mass function in local galaxies are traditionally made at ultraviolet, optical and near-infrared wavelengths, which cannot be probed in dust-obscured galaxies2,3, especially distant starbursts, whose apparent star-formation rates are hundreds to thousands of times higher than in the Milky Way, selected at submillimetre (rest-frame far-infrared) wavelengths4,5. The 13C/18O isotope abundance ratio in the cold molecular gas-which can be probed via the rotational transitions of the 13CO and C18O isotopologues-is a very sensitive index of the stellar initial mass function, with its determination immune to the pernicious effects of dust. Here we report observations of 13CO and C18O emission for a sample of four dust-enshrouded starbursts at redshifts of approximately two to three, and find unambiguous evidence for a top-heavy stellar initial mass function in all of them. A low 13CO/C18O ratio for all our targets-alongside a well tested, detailed chemical evolution model benchmarked on the Milky Way 6 -implies that there are considerably more massive stars in starburst events than in ordinary star-forming spiral galaxies. This can bring these extraordinary starbursts closer to the 'main sequence' of star-forming galaxies 7 , although such main-sequence galaxies may not be immune to changes in initial stellar mass function, depending on their star-formation densities.

Circulating androgen receptor combined with 18F-fluorocholine PET/CT metabolic activity and outcome to androgen receptor signalling-directed therapies in castration-resistant prostate cancer.

The association between choline uptake and androgen receptor (AR) expression is suggested by the upregulation of choline kinase-alpha in prostate cancer. Recently, detection of AR aberration in cell-free DNA as well as early 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) were associated with outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone and enzalutamide. We aimed to make a direct comparison between circulating AR copy number (CN) and choline uptake at FCH-PET/CT. We analysed 80 mCRPC patients progressing after docetaxel treated with abiraterone (n = 47) or enzalutamide (n = 33). We analysed AR CN from plasma samples using digital PCR and Taqman CN assays and total lesion activity (TLA) and metabolic tumor volume (MTV) on FCH-PET/CT at baseline. A meaningful correlation was showed among AR gain and TLA/MTV compared to AR non-gained cases (P = 0.001 and P = 0.004, respectively), independently from type of treatment. Multivariate analysis revealed that AR CN and only TLA were associated with both shorter PFS (P < 0.0009 and P = 0.026, respectively) and OS (P < 0.031 and P = 0.039, respectively). AR gain appeared significantly correlated with choline uptake represented mainly by TLA. Further prospective studies are warranted to better address this pathway of AR-signalling and to identify multiplex biomarker strategies including plasma AR and FCH-PET/CT in mCRPC patients.

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study.

The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration.

Prognostic value of 18F-FDG standard uptake value by integrated PET/CT in the staging of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with generally disappointing results in terms of survival, however, there are occasional long-term survivors probably due to the biologic characteristics of the disease. Standard uptake value (SUV) of [(18)F] Fluorodeoxyglucose (FDG) evaluated by photon emission tomography (PET) is now widely accepted as an indicator of biologic behavior in several malignancies. The aim of this study was to verify whether SUV(max) and SUV(mean) are inversely associated with the prognosis of patients with MPM and whether there was a correlation between grading/disease stage and SUV value. Patients with histologically proven MPM underwent integrated PET and computed tomography (CT) scanning. Patients fasted and received 5.18 MBq of FDG per kilogram of body weight. Based on the maximum Chi-Square method, a SUV(max) of 4.21 (range: 2.30-14.74) and a SUV(mean) of 2.78 (range: 1.80-7.00) were used to classify patients as having a good or poor prognosis, respectively. From January 2004 to March 2010, 27 patients were analyzed: median age was 65 years (range: 54-77) and histologic MPM subtypes were epithelioid (23 patients) and biphasic (4 patients). At a median follow-up of 23 months (range: 1-52), there was no difference in median survival for either high or low SUV(max) [26 months (range: 11-not reached) vs.19 months (range: 12-not reached); p=0.811] or for high or low SUV(mean) [26 months (range: 8-not reached) vs.19 months (range: 11-not reached); p=0.831]. High SUV(max) (p=0.018) was statistically correlated with high-stage disease. There was only a trend towards statistical significance between high-grade disease and high SUV(mean) (p=0.083); no such trend was found between advanced stages and SUV(max) (p=0.268). We observed a significant correlation only between high SUV(max) and high-grade disease. No other relationships between SUV(max) and SUV(mean) with biologic and clinical parameters were found. This is probably due to the patient characteristics and to the non-routine use of 18F-FDG PET/CT to stage rare tumors such as MPM.

A case of carotid artery resection and replacement in advanced laryngeal carcinoma.

Carotid involvement in head and neck tumours carries a poor prognosis and poses an additional challenge to patient management. Tumor fixity and high-definition imaging modalities can suggest, but not determine, carotid wall invasion, which can be proven only by perioperative observation. Conservative management offers no hope of cure or palliation. While radical tumor excision with carotid peeling or resection seems the only chance for prolonging survival, this strategy has not yet unequivocally improved short-term survival. A 74-year-old man with advanced laryngeal carcinoma presented to our unit with preoperative computed tomographic (CT) signs of neoplastic carotid involvement. Radical surgery was planned and partial hypopharyngectomy, total laryngectomy and left neck dissection were performed. Since grossly indurated tissue extended to the lateral surface of the carotid bifurcation, precluding separation from the vessel, carotid vessel resection and saphenous graft repair were carried out. At 6 months after the operation, the patient is presently alive without neurological complications and free of tumor recurrence or distant metastases. This observation supports the view that CT scanning is a valuable method for detecting malignant carotid invasion and that radical surgery, extending resection to the affected carotid segment, can prolong disease-free short-term survival in this patient group.

Fiberoptic endoscopic evaluation of swallowing (FEES): proposal for informed consent.

Fiberoptic endoscopic evaluation of swallowing (FEES) is now a first choice method for studying swallowing disorders on account of the various advantages it offers: easy to use, very well tolerated, allows bedside examination and is economic. Nevertheless, this diagnostic procedure is not without risks, the most probable consequences of which include discomfort, gagging and/or vomiting, vasovagal syncope, epistaxis, mucosal perforation, adverse reactions to topical anaesthetics and laryngospasm. The risks involved with FEES stress the importance of informing the patient of these; this is an important aspect in medicine that necessarily and immediately implies receiving the patient's so-called "informed consent". Informed consent should be obtained not only by means of specific printed forms but also after the patient has had an interview with the physician who will be performing the procedure and who will offer information according to the personal clinical, psychological, cultural and linguistic situation of the patient and in keeping with the type of procedure proposed. In the case of FEES, as with other invasive or non-invasive diagnostic procedures, therefore, routine written and signed consent, together with a patient/physician interview should fulfil what is known as "complete information". In this report, a specific form for informed consent to FEES procedures, is proposed.

Clinical applications of oro-pharyngo-oesophageal scintigraphy in the study of dysphagia.

The diagnostic approach to patients with dysphagia is well established and relies mainly on videofluoroscopy and endoscopy. Oro-pharyngo-oesophageal scintigraphy permits both a functional and a semi-quantitative study of the various stages of swallowing. Moreover, by means of this investigation, it is possible to estimate the amount of inhaled bolus. Oro-pharyngo-oesophageal scintigraphy with 99mTc-nanocolloid has been found to be easy to use, economical, well tolerated and, supplying precise indications regarding the extent of the swallowing disorder, then permits a better clinical definition of the patient. The limitations of swallowing scintigraphy are: poor definition in visualizing anatomic structures and low specificity when used as the only diagnostic test. Scintigraphy plays an important role in the diagnosis and follow-up of dysphagia, and its use, together with other diagnostic techniques, increases diagnostic accuracy. In this study, the role of oro-pharyngo-oesophageal scintigraphy has been analysed in patients with post-surgical, neurological and oesophageal dysphagia.

Swallowing disorders: proposal of a method for forensic medicine assessment.

For a correct classification of dysphagia, morphologic instrumental investigations capable of analysing the anatomical structures of the digestive tract, are undoubtedly essential, but the most important investigations are the functional investigations, such as videofluoroscopy, fiberoptic endoscopic evaluation of swallowing, oro-pharyngo-oesophageal scintigraphy, manometry and pH-metry. Results of these examinations enable us to identify, in patients with dysphagia, the extent of permanent damage, as a consequence of injury to the structures designated to swallowing, must be such that it at least minimally impairs and decreases the relative function, but to a degree that can be detected and, in some manner, measured. From a legal point of view, alterations in swallowing, caused by damage to structures belonging to the respiratory-digestive tract, can be found in crimes against persons and particularly in those involving body injury. In the case of civil, but also in private or social insurance proceedings, it is necessary to distinguish which parameters are to be used as reference for evaluating and quantifying the injury in terms of reimbursement. With the introduction of complete biological well-being, injury is considered as an impairment of the worth and right to enjoy psychological-physical integrity as a quality of life. The criteria currently used internationally take into account the conception of psychological-physical efficiency; nevertheless, in Italian forensic medicine, there is no table that offers a thorough quantification of swallowing modifications, if one excludes oesophageal disorders. Herewith, an evaluation table, dividing oro-pharyngo-oesophageal dysphagia into five, progressively serious classes, is proposed.

Paradoxical vocal cord dysfunction: clinical experience and personal considerations.

Paradoxical vocal cord dysfunction is a nosographic entity that remains to be fully elucidated as far as concerns criteria required for diagnosis and underlying aetiopathogenesis. The disorder manifests with repeated episodes of acute dyspnoea associated with a series of symptoms that may include hoarseness, globus, chest pain and "shortness of breath". A retrospective analysis of cases with acute dyspnoea referred to our Department between June 2004 and June 2005 revealed 3 patients with paradoxical vocal cord dysfunction. In 2 of these 3 cases, concomitant psychiatric morbidity was observed and the third also presented gastro-oesophageal reflux. In one patient, the episodes of dyspnoea were triggered by inspiration of irritating substances. Diagnosis of the condition requires a high level of suspicion, which is confirmed by a laryngoscopic investigation that demonstrates hyperadduction of the true vocal cords and a reduction of at least 50% in the breathing space. From a therapeutic point of view, patients with paradoxical vocal cord dysfunction require, in our opinion, a multidisciplinary approach; in fact, only a team comprising otorhinolaryngologists, phoniatricians, pulmonologists, neurologists, allergologists, psychotherapists and speech therapists is capable of defining the appropriate treatment according to the clinical and psychological characteristics of each individual patient. Our results with speech therapy, focused on respiratory and speech retraining, are reported.

Progressive sensorineural hearing loss in childhood.

A progressive sensorineural hearing loss in childhood, with an extremely variable prevalence (from 4% to 30%), has been reported in the literature. This wide range of reported figures could depend on the different criteria used for identifying the deterioration, the groups, and the examined age ranges. The most frequent etiology of progressive sensorineural hearing loss in childhood includes hereditary causes, both syndromic and nonsyndromic, and developmental and infectious causes, whereas metabolic, toxic, autoimmune, traumatic, and vascular etiologies are less common; however, the origin of the hearing impairment often remains unknown. The population for this study consisted of 178 children with bilateral sensorineural hearing loss who were examined between 1971 and 1993 using audiologic tests. Syndromal genetic hearing loss was excluded from the study. A progressive loss of acuity was found in 11 subjects, with a prevalence of 6.2%. The etiology was hereditary deafness in five patients, congenital infection in one, and congenital inner ear anomaly in another patient; in the last four children the etiology was unknown. Onset of deterioration was after 4 years of age in 73% of the patients. The progressive evolution was binaural in almost all patients (10 of 11) and asymmetric in most, with a tendency to a greater deterioration at the frequencies initially least affected.

Neuro-laryngeal involvement in Churg-Strauss syndrome.

We report our clinical experience in managing a 59-year-old Italian male with Churg-Strauss syndrome (CSS) whose first clinical manifestation was a persistent dysphonia; the patient worked as a mechanic. Video-laryngostroboscopic examination revealed paresis of the right vocal fold with a reduction in adduction together with incomplete glottal closure. Spectrographic and spirometric tests both showed abnormal changes. Laryngeal electromyography revealed neurogenic damage of the right thyroarytenoid and crycoarytenoid muscles. Due to the appearance of typical signs of systemic involvement of CSS as a necrotizing vasculitis, the patient was admitted to the Rheumatology Unit of the University of Pisa. Histologic analysis of a skin lesion on the patient's foot confirmed the diagnosis. Treatment with 6-methylprednisolone quickly brought remission from systemic and laryngeal symptoms, as well as improvement in the results of video-laryngostroboscopic, spectrographic and laryngeal myographic tests.

[Progressive sensorineural hearing loss in childhood]. / Ipoacusia neurosensoriale progressiva nell'infanzia.

Prevalence of progressive sensorineural hearing loss in childhood seems to be extremely variable, as percentages reported range from 4 to 30%. Differences in the criteria employed for identifying the deterioration, in the groups of patients, and the age range, could explain this wide range of reported figures. The etiology of the progressive sensorineural hearing loss in infants can be hereditary or acquired. Hereditary causes are divided into syndromic and non-syndromic, whereas the acquired causes include congenital or acquired infection (syphilis, cytomegalovirus, rubella virus and toxoplasma infections, bacterial meningitis and acquired viral infections) and congenital inner ear anomalies (Mondini's dysplasia, large vestibular aqueduct, large cochlear aqueduct). Other acquired causes such as disorders of the metabolism, chronic use of ototoxic drugs, autoimmune diseases, perilymphatic fistula and head or acoustic trauma are less common. The age of onset of deterioration shows a great variability because even the congenital hearing losses may occur late after birth. The progressive evolution seems to be binaural in most patients, but more commonly it presents interaural differences, and when the hearing deficit is initially asymmetrical the deterioration is usually greater in the ear which appeared least affected in the first audiogram. Furthermore, at the different frequencies, there is a tendency to a greater deterioration at the frequencies initially least affected, but some authors are not in agreement because they report a uniform pattern of progression in the range of 0.5 to 4 kHz with no modification of the audiometric shape in most of the examined patients.

Simultaneous dobutamine stress echocardiography and dobutamine scintigraphy (99mTc-MIBI-SPET) for assessment of coronary artery disease.

BACKGROUND: Simultaneous dobutamine stress echocardiography (DSE) and 99Tc-MIBI-SPET (DMS) for the evaluation of the presence and the extent of coronary artery disease (CAD) were assessed for a head to head comparison regarding the diagnostic acuracy of the two rests. METHODS AND RESULTS: Forty-five consecutive patients (33 males and 12 females: 53 +/- 6.8 yr.) underwent exercise electrocardiography and simultaneous dobutamine stress echocardiography and MIBI-SPET imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiogram the pre-test probability for coronary artery disease (Diamond's algorithm) was low (45.6 +/- 12.7%). The overall specificity, sensitivity and predictive accuracy of Echo-dobutamine stress test for diagnosis of the presence or absence of CAD were: specificity 82%, sensitivity 76%, diagnostic accuracy 80%, positive predictive value 90%, negative predictive value 40%. The overall specificity, sensitivity and predictive accuracy of MIBI-SPET-dobutamine test for diagnosis of the presence or absence of CAD were: specificity 86%, sensitivity 87%, diagnostic accuracy 84%, positive predictive value 97%, negative predictive value 54%. MIBI-SPET-dobutamine test showed a significantly higher sensitivity in comparison with ECHO-dobutamine test (P < 0.05). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy. Nevertheless the SPET model showed a higher sensitivity in comparison with DSE model, essentially in the presence of a lower extent of CAD and during submaximal test.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease.

BACKGROUND: The incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves. METHODS AND RESULTS: Forty-five consecutive patients (33 men and 12 women; 53 +/- 6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamond's algorithm) was low (45.6% +/- 12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3% +/- 10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4% +/- 4.3% (p < 0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3% +/- 5.5% (p < 0.003), a level that appeared significantly higher than that of model 2 (p < 0.016). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

Tumor targeting by intra-arterial infusion of 5-[123I]iodo-2'-deoxyuridine in patients with liver metastases from colorectal cancer.

UNLABELLED: We previously showed the tumor-targeting potential of the 125I-labeled thymidine analog 5-iodo-2'-deoxyuridine (IUdR) injected intratumorally in patients with high tumor-cell kinetics. In this study, we evaluated the tumor incorporation of [123I]IUdR infused intra-arterially in patients with liver metastases from colorectal cancer. METHODS: Iodine-123-IUdR (110-300 MBq, 3-8 mCi, specific activity, 150-200 Ci/mumole) was infused into the hepatic artery of 16 patients with inoperable liver metastases over 30-45 min through a permanent intra-arterial catheter. A dynamic sequence during infusion, spot images, whole-body scans and SPECT acquisitions were recorded up to 42 hr. Blood and urine samples were obtained for biodistribution and HPLC analyses. RESULTS: In the 14 patients with adequate tumor perfusion patterns, tumor uptake reached 2%-17.6% ID at the end of infusion. After a washout phase that lasted 18-20 hr, incorporated radioactivity remained steadily associated with the tumor lesions until at least 42 hr after infusion (about 1.4%-11.1% ID). HPLC analysis indicated a virtually 100% first-pass hepatic deiodination of unincorporated [123I]IUdR (about 80%-95% ID recovered in the 42-hr urine). No significant uptake was detected in the bone marrow or in other normal dividing tissues. CONCLUSION: These results encourage further studies to enable dosimetric estimates, optimization of dose regimens, and examination of the therapeutic potential of Auger-electron-emitter-labeled IUdR in cancer therapy utilizing this type of approach.

[111In-DTPA-D-Phe]-octreotide scintigraphy in functioning and non-functioning pituitary adenomas.

Scintigraphy with [111In-DTPA-D-Phe]-octreotide is a recently developed technique for imaging somatostatin receptors in many neuroendocrine tumors. A good correlation between high [111In-DTPA-D-Phe]-octreotide uptake and the response to octreotide therapy has been proved in TSH- and GH-secreting pituitary adenomas, while few and conflicting scintigraphic data on somatostatin receptors in non-functioning tumors have been reported in the literature. The present study presents the results obtained with [111In-DTPA-D-Phe]-octreotide scintigraphy in thirteen patients with GH-secreting pituitary adenoma, four patients with inappropriate TSH-secretion and twelve patients with non-functioning pituitary adenoma. Twelve out of the 13 patients with GH-secreting pituitary adenomas had a positive scan; moreover, in 5/6 patients with a GH-secreting microadenoma (tumor size range 5-8 mm) a positive scan was found. Two TSH-secreting macroadenomas had a positive scan while a negative scan was obtained for a TSH-secreting pituitary microadenoma and in a patient with non-neoplastic, inappropriate secretion of TSH. Finally, only 2/12 patients with non-functioning pituitary adenoma showed a positive scan. In conclusion, [111In-DTPA-D-Phe]-octreotide scintigraphy is a useful tool to confirm the presence of somatostatin receptors in selected patients with GH- and TSH-secreting pituitary adenoma. The role of [111In-DTPA-D-Phe]-octreotide scintigraphy in non-functioning pituitary tumors remains to be established, but it could be useful for octreotide treatment in patients who refuse surgery or who are poor surgical candidates.