Tc 99m-Sestamibi scintimammography in the differentiation of benign and malignant breast microcalcifications.

The capability of the mammography-scintimammography combination to distinguish between benign and malignant isolated clusters of breast microcalcifications is discussed. Scintimammography using Tc 99m-Sestamibi was performed in 97 women with an isolated cluster of microcalcifications on mammograms. Seventy-two women had final histopathologic diagnoses (24 cancer and 48 benign pathology). The other 25 patients had follow-up to 3 years. The results of mammography, scintimammography and mammography-scintimammography combination were divided into five groups, based on the suspicion of malignancy. The sensitivity, specificity, false negative fraction, false positive fraction, predictive positive value, predictive negative value and diagnostic accuracy were calculated varying the diagnostic threshold. The Receiver Operating Characteristic (ROC) statistical technique was employed to compare the diagnostic value of mammography to mammography-scintimammography combination. The area under the ROC curves was calculated by the Wilcoxon statistic without any hypothesis on data distribution. The detected difference between areas under the mammography ROC curve (area=0.854, standard error=0.049) and mammography-scintimammography ROC curve (area=0.897, standard error 0.033) was statistically significant (P>0.05, one tail). The area under a ROC curve represents the probability that a randomly chosen diseased or non-diseased subject could be correctly classified. From this point of view this paper demonstrates that, if properly used, scintimammography can add to mammography in the characterization of an isolated cluster of microcalcifications, even if it is not able to replace FNAB and core biopsy.

Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry.

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.

Gamma probe-guided thoracoscopic surgery of small pulmonary nodules.

Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for the diagnosis and treatment of peripheral pulmonary nodules. We developed a new radioguided surgical technique for the detection during VATS of pulmonary nodules smaller than 2 cm, situated deep in the lung parenchyma and neither visible nor palpable with endoscopic instruments. The procedure is divided into two phases. Two hours before surgery 0.3 ml of a solution composed of 0.2 mL of 99mTc-labeled human serum albumin microspheres (5-10 MBq) and 0.1 mL of non-ionic contrast is injected into the lesion under CT guidance. Then the patient is submitted to VATS. During thoracoscopy a collimated probe of 11 mm diameter connected to a gamma ray detector is introduced via an 11.5 mm trocar and the pleural surface of the suspected area is scanned. A hot spot indicates the presence of the radiolabeled nodule and hence the area to be resected. We treated 39 patients with small pulmonary nodules (mean size, 8.3 mm; range, 4-19 mm). The patients were 27 men and 12 women (mean age, 60.8 years; range, 13-80 years). Nineteen patients had a history of synchronous or metachronous malignancy. In all cases the nodule was detected and resected and the resection margins were pathologically free of tumor. Histological examination showed 21 benign and 18 malignant lesions (7 metastases and 11 primary lung cancers). Nine patients with a frozen section-based histopathological diagnosis of lung cancer without functional contraindications underwent a completion lobectomy by open surgery in the same surgical session. In conclusion, the radiolocalization of small pulmonary nodules by gamma probe during VATS is a safe and easy procedure, with fewer complications and a lower failure rate than other localization techniques.

Investigation on the iodination reaction of methylene blue by liquid chromatography-mass spectrometry with ionspray ionisation.

Radioactive iodine (131I and 123I) labelled methylene blue is used for the early diagnosis of melanoma metastases. We studied the iodination reaction of methylene blue (using "cold" iodine) in order to characterise the iodination product(s) as far as number and position of iodine atoms introduced on the aromatic ring(s) is concerned. The reaction was carried out under the same experimental conditions used for the radioactive one, that is in a large excess of methylene blue. The ionspray HPLC-MS analysis of the reaction mixture showed that the iodinated methylene blue was present only in a very small amount and the main iodinated product was a demethylated one, coming out from the iodination of an impurity azure B. We also studied the iodination reaction of azure B in order to better explain the reaction pathway. Commercial azure B contains impurities of methylene blue and all the possible demethylated derivatives. HPLC-MS analysis of the reaction mixture allowed a complete characterisation of the iodinated and bis-iodinated products.

[Transmyocardial revascularization with a holmium laser: preliminary results]. / Rivascolarizzazione transmiocardica con laser ad olmio: risultati preliminari.

BACKGROUND: Transmyocardial laser revascularization (TMLR) aims to improve perfusion of the ventricular wall via laser-created transmural channels. We present the results of TMLR with a holmium laser as sole therapy in patients with angina refractory to medical treatment and extensive coronary artery disease unsuitable for angioplasty or coronary artery by-pass grafting. METHODS: From November 1995 to February 1997, twenty-two patients underwent isolated TMLR with a holmium laser. Five patients (23%) were female; the mean age was 67 +/- 7 years (range 53 to 74 years). Previous myocardial revascularization procedures had been performed in 17 patients (77%). Mean preoperative angina class was 3.4 +/- 0.5 and unstable angina was present in 7 patients (32%). RESULTS: There were no hospital deaths. The only postoperative complications were transient supraventricular arrhythmias in 6 patients (27%). Each patient received a mean of 33 +/- 8 channels in 27 +/- 13 minutes. There were two late deaths, 40 days and 4 months after TMLR, due to stroke and myocardial infarction, respectively. Mean follow-up duration was 8 +/- 5 months (range 40 days-15 months). The mean number of hospitalizations due to angina fell from 4.9 +/- 1.5 in the 6 months before TMLR to 1.5 +/- 1.0 in the 6 months following surgery (p < 0.001). At follow-up, mean angina class had significantly improved (1.8 +/- 0.6, p < 0.001), as well as effort tolerance, which increased from a mean of 3.5 +/- 1.4 minutes to 5.1 +/- 1.7 minutes (p = 0.01). 201Tl SPECT at 3 and 6 months did not show any significant changes in the segmental perfusion of the lased and unlased areas. CONCLUSIONS: TMLR with a holmium laser is a simple procedure with low operative mortality and morbidity. Short-term results confirm that clinical improvement is obtained in most patients, although this is not supported by significant changes in myocardial perfusion at short-term follow-up.

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.

Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.

Pulmonary retention of iodobenzyl-propanediamine in humans. Effect of cigarette smoking.

N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM), a synthetic basic compound with high affinity for lung tissue of various animal species, was labeled with 123I and injected into normal smokers (n = 9) and into asymptomatic smokers (n = 9). Time/activity curves were recorded for 90 min by gamma camera. HIPDM lung clearance was described by two exponential components. In smokers, the mean time of the first component, 10 +/- 1.4 min (mean +/- SEM), did not significantly differ from that of nonsmokers (9.7 +/- 0.9 min), whereas the mean time of the second component (12.9 +/- 0.6 h) was longer than that of nonsmokers (6.7 +/- 0.2 h). The intercept to the ordinate of the second exponential component was significantly higher in smokers (90.3 +/- 1.5%) than in nonsmokers (80.7 +/- 1.9%). Control studies in rabbits showed that, 2 min after intravenous injection, 95% of HIPDM is taken up by the lung; time/activity curves were similar to those obtained in humans. The longer pulmonary persistence of HIPDM in smokers may reflect an increased number of cellular binding sites or may be the expression of hindered HIPDM biotransformation. The rabbit can be used as a model to further investigate HIPDM kinetics in relation to lung dysfunction.