A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. RESULTS: A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). CONCLUSION: The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. CLINICAL TRIAL NUMBER: EudraCT# 2011-002564-24.

Use of QT intervals for a more accurate diagnose of syncope and evaluation of syncope severity.

BACKGROUND: This study aimed to evaluate the use of QT intervals, their diagnostic predictive value in patients with syncope and their relationship with syncope severity. METHODS: One hundred and forty nine patients with a diagnosis of syncope were admitted to Internal Medicine departments at the University of Palermo, Italy, between 2006 and 2012, and 140 control subjects hospitalised for other causes were enrolled. QT maximum, QT minimum, QTpeak, QT corrected, QT dispersion and Tpeak-to-Tend interval were compared between two groups. The paper medical records were used for scoring with San Francisco Syncope Rule (SFSR), Evaluation of Guidelines in SYncope Study (EGSYS) score and Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score. RESULTS: Mean QTc (p < 0.0005), mean QTmax (p < 0.0005), mean QTdisp (p < 0.0005), mean QTpeak (p = 0.005) and mean TpTe (p = 0.018) were significantly longer in patients with syncope compared with control subjects. A QTc > 424.8 ms (sensibility: 81.88 - specificity: 57.86) showed the greatest predictive value for diagnosis of syncope. On the EGSYS score and on the OESIL score, QTc was significantly prolonged in high-risk patients compared with low-risk patients. On the San Francisco Syncope Rule, QTc and QTdisp were significantly prolonged in high-risk patients compared with low-risk patients. CONCLUSION: Mean QTc, mean QTdisp, mean TpTe, mean QTmax and mean QTpeak were significantly longer in patients with syncope compared with control subjects. Furthermore, prolonged QTc and QTdisp were associated with major severe syncope according to San Francisco Syncope Rule, EGSYS and OESIL risk scores.

Acute myocardial infarction caused by multivessel spontaneous coronary artery dissection in a postpartum woman.

Spontaneous coronary artery dissection is a rare cause of acute ischemic coronary events and sudden cardiac death. It usually occurs in young women not experiencing traditional risk factors for coronary artery disease during pregnancy or postpartum period. The pathophysiology of spontaneous arterial dissection remains uncertain and the management may be challenging. Herein, we report a case of a 41-year woman with no apparent cardiovascular risk factors, who underwent a successfull in vitro fertilization and embryo transfer with a subsequent at term cesarean section of a twin pregnancy. Six days after delivery, she presented with anterior ST-segment elevation myocardial infarction. Coronary angiography revealed dissection of all three coronary arteries with involvement of left main stem, which was successfully treated with percutaneous coronary intervention and drug-eluting stents implantation. The peculiarities of the case, toghether with the treatment strategy and the clinical and angiographic six-month follow-up are discussed.

Decoding bladder state from pudendal intraneural signals in pigs.

Neuroprosthetic devices used for the treatment of lower urinary tract dysfunction, such as incontinence or urinary retention, apply a pre-set continuous, open-loop stimulation paradigm, which can cause voiding dysfunctions due to neural adaptation. In the literature, conditional, closed-loop stimulation paradigms have been shown to increase bladder capacity and voiding efficacy compared to continuous stimulation. Current limitations to the implementation of the closed-loop stimulation paradigm include the lack of robust and real-time decoding strategies for the bladder fullness state. We recorded intraneural pudendal nerve signals in five anesthetized pigs. Three bladder-filling states, corresponding to empty, full, and micturition, were decoded using the Random Forest classifier. The decoding algorithm showed a mean balanced accuracy above 86.67% among the three classes for all five animals. Our approach could represent an important step toward the implementation of an adaptive real-time closed-loop stimulation protocol for pudendal nerve modulation, paving the way for the design of an assisted-as-needed neuroprosthesis.

Coronary stenting for ST-elevation myocardial infarction vs. other indications in patients on oral anticoagulation: any difference in in-hospital management and outcome?

AIM: The aim of this paper was to compare the in-hospital management and outcome of patients on oral anticoagulation (OAC) undergoing coronary artery stenting (PCI-S) for ST-elevation myocardial infarction (STEMI) vs. other indications. METHODS: One hundred and sixteen patients on OAC at the time of PCI-S who were prospectively enrolled in a multi-center, observational registry, were evaluated. Patients were segregated according to whether PCI-S was performed for STEMI (group 1) or other indications, such as non ST-elevation acute coronary syndromes, stable angina, silent ischemia, etc. (group 2), and the pharmacological and procedural management, as well as the in-hospital outcome, were compared. RESULTS: No significant differences were observed in vascular access site, sheath size and type of stent implanted, nor was significantly different the use of glycoprotein IIb/IIIa inhibitors, and the use and dose of intravenous unfractionated heparin. Although not statistically different, the in-hospital occurrence of death (3.7% vs. 1.1%; OR 3.3; 95% confidence intervals [CI] 0.2-56.0), stent thrombosis (3.7% vs. 1.1%; OR 3.3; 95% CI 0.2-56.0) and major bleeding (7.4% vs. 2.2%; OR 3.4; 95% CI 0.4-25.9) was consistently about 3-fold higher in group 1. CONCLUSION: The in-hospital pharmacological and procedural management of OAC patients undergoing PCI-S for STEMI vs. other indications appears not different. Although not significantly different however, the in-hospital occurrence of major bleeding, as well as of death and stent thrombosis, appears substantially higher in patients treated for STEMI, warranting therefore further larger, prospective studies.

2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography Deauville scale and core-needle biopsy to determine successful management after six doxorubicin, bleomycin, vinblastine and dacarbazine cycles in advanced-stage Hodgkin lymphoma.

BACKGROUND: The clinical impact of the positivity of the Deauville scale (DS) of positron emission tomography (PET) performed at the end of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in patients with advanced Hodgkin lymphoma (HL), in terms of providing rationale to shift poor responders onto a more intensive regimen, remain to be validated by histopathology. PATIENTS AND METHODS: This prospective trial involved patients with stage IIB/IV HL who after six ABVD cycles underwent PET (PET6) and core-needle cutting biopsy (CNCB) of 2-deoxy-2[F-18] fluoro-d-glucose (FDG)-avid lymph nodes. Patients received high-dose chemotherapy/autologous haematopoietic stem cell rescue (HDCT/AHSCR) if CNCB was positive for HL, alternatively, if CNCB or PET was negative, received observation or consolidation radiotherapy (cRT) on residual nodal masses, as initially planned. The end-point was 5-year progression-free survival (PFS). RESULTS: In all, 43 of the 169 (25%) evaluable patients were PET6 positive (DS 4, 32; DS 5, 11). Among them, histology showed malignancy (HL) in 100% of DS 5 scores and in 12.5% of DS 4 scores. Fifteen patients with positive biopsy received HDCT/AHSCR, whereas 28 patients with negative biopsy, as well as 126 patients with negative PET6, continued the original plan (cRT, 78 patients; observation, 76 patients). The 5-year PFS in the negative PET6 group, negative biopsy group and positive biopsy group was 95.4%, 100% and 52.5%, respectively. CONCLUSION: DS positivity of end-of-ABVD PET in advanced HL carried a certain number of CNCB-proven non-malignant FDG-uptakes. The DS 4 scores which were found to have negative histology appeared to benefit from continuing the original non-intensive therapeutic plane as indicated by the successful outcome in more than 95% of them by obtaining similar 5-year PFS to the PET6-negative group. By contrast, the DS 5 score had consistently positive histology and was associated with unsuccessful conventional therapy, promptly requiring treatment intensification or innovative therapeutic approaches.

Comparison of two dedicated 'in beam' PET systems via simultaneous imaging of (12)C-induced beta(+)-activity.

The selective energy deposition of hadrontherapy has led to a growing interest in quality assurance techniques such as 'in-beam' PET. Due to the current lack of commercial solutions, dedicated detectors need to be developed. In this paper, we compare the performances of two different 'in-beam' PET systems which were simultaneously operated during and after low energy carbon ion irradiation of PMMA phantoms at GSI Darmstadt. The results highlight advantages and drawbacks of a novel in-beam PET prototype against a long-term clinically operated tomograph for ion therapy monitoring.

Froggy mouth: a new myofunctional approach to atypical swallowing.

INTRODUCTION: Atypical swallowing has a high incidence in adult and child populations. The treatment of the latter is generally achieved by the adoption of orthodontic appliances in conjunction with speech therapy. The aim of this article is to describe the clinical protocol of Froggy Mouth, an innovative myofunctional appliance designed to correct the atypical swallowing. MATERIALS AND METHODS: The Froggy Mouth appliance has been tested by the authors Di Vecchio at the Orthognatodontics department of Fatebenefratelli San Pietro Hospital in Rome, Italy, and by Manzini at the Orthodontics department of Carlo Poma Hospital in Mantova, Italy. This article will illustrate the clinical protocol of the appliance with therapeutic indications, clinical phases, instruction and patients and parents motivation and follow-up results. RESULTS: Froggy Mouth has proven effective in the correction of atypical swallowing, from both the clinical and the functional standpoints. The fastest and most predictable results were obtained in patients during their physiological developmental age. This appliance, compared to the traditional logopaedic therapy, requires less commitment in terms of time for the patient (only 15 minutes per day), with more predictable and durable results over time. CONCLUSIONS: The clinical evidences indicate that the Froggy Mouth is effective in the myofunctional correction of the atypical swallowing mechanism, providing the clinician a new therapeutic approach for neuromuscular re-training of atypical deglutition and dysfunctional deglutition in patients during their growth phase. However, further scientific evidences are needed to support the results of this investigation.

Increasing the germination percentage of a declining native orchid (Himantoglossum adriaticum) by pollen transfer and outbreeding between populations.

The declining native orchid Himantoglossum adriaticum H. Baumann is a European endemic of priority interest (92/43/ EEC, Annex II). Northern Italian populations of H. adriaticum are small and isolated, with depressed seed set. Given the important implications for plant population conservation, we tested the hypothesis that artificial pollen transfer (hand-pollination) and outbreeding between populations increases fruit set and seed germination percentage. The background fruit set and in vitro germination rates were determined for ten reference populations. An artificial cross-pollination experiment included (a) pollen transfer from one large population to two small and isolated populations; (b) pollen transfer between two small but not isolated populations; (c) within-population pollen transfer (control). All seeds were sown on a modified Malmgren's medium and cultured in a controlled environment. Germination percentage was compared using a Kruskal-Wallis anova. The background fruit set (mean = 18%) and germination (<5%) rates were consistently low across populations. Fruit set after hand-pollination was consistently 100%. Pollen transfer from the largest population to smaller populations resulted in an increase in total germination ranging from 0.9% to 2.9%. The largest increase in germination occurred between small-sized and less isolated populations (from 1.7% to 5.1%). The results of pollen transfer between the small populations are particularly encouraging, as the mean increase in germination was almost four times that of the control. Outbreeding can be considered a valuable tool to increase genetic flow and germination in natural populations, limit the accumulation of detrimental effects on fitness driven by repeated breeding with closely-related individuals, thereby increasing the possibility of conservation of rare or endangered species.

Difficulties in conducting pure academic research, obstacles in data collection and quality of informations: The example of the INTERCEPTOR study.

PURPOSE/OBJECTIVE: On September 2009: We started a randomized multicenter phase III study comparing chemoradiation (CRT) (Aldestein RTOG regimen) versus induction chemotherapy followed by Cetuximab radiation (IBRT). The main study's aim was comparison of overall survival but no formal analyses have been made between the two arms because of low accrual and high amount of missing data. The goal of this paper is to identify the reasons of difference in accrual and quality of data among participating centers. MATERIAL/METHODS: Statistic: We correlated data collection quality with relevance of the centers, accrual and number of scientific papers (both specific on HNC and other topics) of each PI. We created an HNC publishing score dividing the number of HNC specific papers for the overall number of published papers. RESULTS: We observed a strong difference in the accrual of pts as well as in the quality of data among the participating centers. The accrual was independent from the quality of data since some centers with low accrual produced high quality data with an excellent follow up. We found a correlation among both number of published papers of each PI and HNC publishing score with the quality of data. CONCLUSION: The study demonstrated that expertise in HNC is important not only to ensure a better outcomes but also to provide high quality data in phase III trials.

Usefulness of [111In-DTPA0] octreotide scintigraphy in a family with von Hippel-Lindau disease.

The identification of patients with von Hippel-Lindau (VHL) disease dictates accurate genetic counseling of family members, whereas screening for early detection of visceral and neurological involvement is usually performed by a combination of radiological and nuclear medicine techniques such as ultrasonography or contrast-enhanced computed tomography of the upper abdomen, magnetic resonance imaging of the central nervous system and 131I-metaiodobenzylguanidine-scintigraphy. The role of 111-indium-diethylenetriaminepentaacetic acid [111In-DTPA0] octreotide scintigraphy in this clinical context has never been investigated. Here, we report imaging findings in a VHL patient and in 3 consecutive family members undergoing clinical and radiological screening that included [111In-DTPA0] octreotide scintigraphy in addition to the above-mentioned procedures. Somatostatin receptor expression was investigated in vitro by immunohistochemistry in pancreatic tumor sections. On the basis of in vivo and in vitro findings, octreotide long-acting release treatment followed by 90Y-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA0)-Tyr3-octreotide led to a lack of progression in this patient although this result is a possibility which needs to be proved by further investigation and longer follow-up. The results of this study suggest that [111In-DTPA0] octreotide scintigraphy may be helpful in the routine work-up of VHL patients for diagnostic and therapeutic purposes.

Venture wire control catheter in percutaneous treatment of complex coronary bifurcation. A case report.

We present a case report of a man with atherosclerotic involvement of a left main trifurcation treated by the Venture wire control catheter. The patient was submitted to primary percutaneous transluminal coronary angioplasty (PTCA) in a primary center for acute occlusion of the left anterior descending artery, then he was transferred to our tertiary center to perform left main trifurcation revascularization that was unsuccessful by traditional approach. In our high volume center (operator >600 PTCA/year) as well, the attempts at crossing the lesion with a number of different guidewires failed because of the extreme angulation of the circumflex artery. At last, a successful attempt was reached using the Venture wire control, a low profile catheter with a tip that can be deflected up to 90 degrees . Once the lesion was crossed and wiring of other branches obtained, crush stenting of the left anterior descending artery and intermediate ramus and T-stent of the circumflex artery were performed with an optimal angiographic result.

Use of Impella Recover 2.5 left ventricular assist device in patients with cardiogenic shock or undergoing high-risk percutaneous coronary intervention procedures: experience of a high-volume center.

AIM: Percutaneous coronary interventions are increasingly applied to high-risk patients. The availability of hemodynamic support devices offers a promising option to prevent and treat low-output syndrome in these patients. The aim of this study was to evaluate the feasibility, safety and efficacy of the Impella Recover'' LP 2.5 left ventricular assist device in patients with cardiogenic shock or undergoing high-risk percutaneous coronary interventions. METHODS: Eleven patients presenting cardiogenic shock (N=6) or scheduled for high-risk percutaneous revascularization (N=5) were evaluated. The Impella pump was successfully implanted in all patients, except one. When implanted, the device was correctly positioned in the left ventricle and remained in a stable position. RESULTS: Bleedings occurred in 7 patients (5 of them presented cardiogenic shock), while renal failure and severe thrombocytopenia were observed in 4 and 1 patients respectively, all with cardiogenic shock. During high-risk procedures, the Impella pump succeeded in obtaining hemodynamic stability, while in only two patients with cardiogenic shock the device determined a significant improvement of hemodynamic variables. All elective patients and two patients with cardiogenic shock were discharged from the hospital and were still alive at 30-day follow-up. CONCLUSION: These data, although preliminary due to the limited sample size, demonstrated the feasibility, safety and efficacy of the Impella Recover LP 2.5 during high-risk percutaneous procedures, even though the benefits of prophylactic deployment of such a system have to be further investigated. The use of Impella Recover LP 2.5 in patients with cardiogenic shock is feasible and safe, however it maybe insufficient in reversing an advanced cardiogenic shock which, probably, has to be treated with more powerful left ventricular assist devices.

Experimental validation of the filtering approach for dose monitoring in proton therapy at low energy.

The higher physical selectivity of proton therapy demands higher accuracy in monitoring of the delivered dose, especially when the target volume is located next to critical organs and a fractionated therapy is applied. A method to verify a treatment plan and to ensure the high quality of the hadrontherapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear reactions between protons and nuclei in the tissue during irradiation producing beta(+)-emitting isotopes. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution; this is the reason why, at the present time, the verification of depth dose profiles with PET techniques is limited to a comparison between the measured activity and the one predicted for the planned treatment by a Monte Carlo model. In this paper we test the feasibility of a different scheme, which permits to reconstruct the expected PET signal from the planned radiation dose distribution along beam direction in a simpler and more direct way. The considered filter model, based on the description of the PET image as a convolution of the dose distribution with a filter function, has already demonstrated its potential applicability to beam energies above 70 MeV. Our experimental investigation provides support to the possibility of extending the same approach to the lower energy range ([40, 70] MeV), in the perspective of its clinical application in eye proton therapy.

Pollination networks along the sea-inland gradient reveal landscape patterns of keystone plant species.

Linking the functional role of plants and pollinators in pollination networks to ecosystem functioning and resistance to perturbations can represent a valuable knowledge to implement sound conservation and monitoring programs. The aim of this study was to assess the resistance of pollination networks in coastal dune systems and to test whether pollination interactions have an explicit spatial configuration and whether this affect network resistance. To this aim, we placed six permanent 10 m-wide belt transects. Within each transect we placed five plots of 2 m x 2 m, in order to catch the different plant communities along the dune sequence. We monitored pollination interactions between plants and pollinators every 15 days during the overall flowering season. The resulting networks of pollination interactions showed a relatively low degree of resistance. However, they had a clear spatial configuration, with plant species differently contributing to the resistance of pollination networks occurring non-randomly from the seashore inland. Our results evidenced that beside contributing to the creation and maintenance of dune ridges, thereby protecting inland communities from environmental disturbance, plant species of drift line and shifting dune communities have also a crucial function in conferring resistance to coastal dune pollination networks.

Leptin and its receptor: can they help to differentiate chromophobe renal cell carcinoma from renal oncocytoma?

One of the challenges in differentiating chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) is overlapping morphology between the two subtypes. The aim of this study was to investigate the usefulness of expression of leptin (Ob) and its receptor (ObR) in discriminating chRCC from RO. Sections from paraffin-embedded, formalin-fixed tumour nephrectomy specimens of 45 patients, made up of 30 chRCC (15 eosinophilic variant and 15 non-eosinophilic variant) and 15 RO, were used in this study. Samples (30) of clear cell RCC (ccRCC), the most common histological subtype, were used to verify staining patterns found by others in our cohort of Australasian patients. Matched morphologically normal non-cancer kidney tissues were included for each specimen. Sections were batch-immunostained using antibodies against Ob and ObR. Stained sections were digitally scanned using Aperio ImageScope, and the expression pattern of Ob and ObR was studied. In this cohort, male to female ratio was 2:1; median age was 64 (45-88 years); and median tumour size was 3.8 cm (range 1.2-18 cm). There were 47 (62.7%) T1, seven T2, 20 T3 and one T4 stage RCC. Two patients with ccRCC presented with metastases. Nuclear expression of Ob was significantly higher in RO compared with chRCC. The increased nuclear expression of Ob in RO compared with chRCC may be a useful aid in the difficult histological differentiation of RO from chRCC, especially eosinophilic variants of chRCC.

Human urokinase receptor concentration in malignant and benign breast tumors by in vitro quantitative autoradiography: comparison with urokinase levels.

We measured the tissue concentration of human urokinase receptor (uPAR) in 22 breast carcinomas and 9 benign breast lesions using in vitro quantitative autoradiography. Tissue sections were incubated with increasing concentrations of 125I-pro-urokinase in the presence or absence of unlabeled competitor. Breast carcinomas were found to contain 5 times more uPAR than benign breast lesions with respect to their protein content [523 +/- 72 versus 108 +/- 20 (SE) fmol/mg (P < 0.001)]. Simultaneous quantitation of urokinase (uPA) by immunoenzymatic assay on tissue extracts from the same specimens showed that breast carcinomas also contain 19 times more uPA than benign tumors (611 +/- 134 versus 32 +/- 8 fmol/mg) (P < 0.01). The reliability of quantitative autoradiography measurements was confirmed by uPAR cross-linking assay on membrane fraction from either U937 histiocytic lymphoma cells or breast carcinomas and immunoperoxidase staining with an anti-uPAR antibody on tumor sections. Also, immunoperoxidase staining with an anti-uPA monoclonal antibody showed that uPA is indeed localized on the plasma membrane of epithelial tumor cells in confined areas of breast carcinomas whereas cells from benign breast lesions were devoid of uPA under the same experimental conditions. In conclusion, our findings support the hypothesis that uPAR plays a central role in the acquisition of an invasive phenotye and favor its potential use as a prognostic factor in patients with breast carcinoma.

Measurement of local Mr 97,000 and 250,000 protein antigen concentration in sections of human melanoma tumor using in vitro quantitative autoradiography.

An assay method that uses 125I-labeled monoclonal antibody (MoAb) and in vitro quantitative autoradiography was developed to determine the local concentration of tumor-associated antigens in tissue sections. Human melanoma biopsy specimens were evaluated for the expression of the Mr 97,000 and 250,000 protein antigens using MoAb-96.5 and MoAb-9.2.27, respectively. Tissue sections were incubated in solutions of increasing concentration of 125I-labeled MoAb with or without an excess of unlabeled antibody. Quantitative autoradiography was performed on the sections and compared with 125I standards to determine tumor-bound radioactivity and calculate bound pmol of MoAb per g of tumor. The total binding, nonsaturable binding, and specific binding of 125I-labeled MoAb to tumor were then computed. Specific binding of MoAbs to tumor tissue was saturable in all antigen-positive tumors. The maximal concentration of specific binding of antibody to tissue (Bmax) represented the tissue antigen concentration. Estimates of the Ka of antigen/antibody binding were also made. The reliability of the measurements was confirmed by testing sections from mixtures of antigen-positive and antigen-negative cells.

Local distribution and concentration of intravenously injected 131I-9.2.27 monoclonal antibody in human malignant melanoma.

Regional measurements of 131I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of 131I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.