13N-ammonia rest/stress PET: folic acid improves global coronary vasoreactivity in coronary artery disease patients with normal or elevated homocysteine levels.

AIM: Hyperhomocysteinaemia (Hhcy) is known to be an independent risk factor for vascular disease. Coronary flow reserve (CFR) measured by positron emission tomography (PET) is a sensitive method to monitor the effects of pharmacologic interventions in Hhcy. We assessed coronary vascular reactivity by PET in patients with coronary artery disease (CAD) dependent on their homocysteine (Hcy) levels before and under high dose folic acid supplementation therapy (FAST). PATIENTS, METHODS: Twelve patients with CAD underwent rest/adenosine (13) N-ammonia PET for quantification of myocardial blood flow (MBF) and CFR before and after nine weeks FAST (10 mg/day). RESULTS: Folate levels increased from 21 +/- 6 to 210 +/- 34 microg/l (+900%, p < 0.0001) while Hcy levels decreased from 12.1 +/- 3.6 to 9.1 +/- 3.1 micromol/l ( - 25%; p < 0.01). Global resting MBF remained nearly unchanged after FAST, while stress MBF (from 2.61 +/- 0.93 to 3.25 +/- 1.15 ml/g/min; p = 0.05) and CFR (from 3.00 +/- 0.76 to 3.72 +/- 0.93 ml/g/min; p < 0.05; +24%) significantly increased in patients with normal and elevated Hcy levels (cut off 12 micromol/l). An inverse relation was found between Hcy and CFR (R = - 0.53; p = 0.08) and between Hcy and MBF at rest (R = - 0.62; p < 0.05) at baseline conditions, not persisting after FAST. CONCLUSION: Coronary vascular reactivity can be improved by FAST in patients with CAD and normal or elevated Hcy levels. FAST might lower an increased cardiovascular risk in CAD patients possibly by mechanisms that are not related to Hcy.

Should lidocaine be avoided for local anesthesia in radiation synovectomy?

AIM: Leakage is of major concern when performing radiation synovectomy. Although post-treatment immobilization was provided, extra-articular leakage of radioactivity has occasionally been observed in patients receiving local anesthesia in the course of radiation synovectomy. This study was performed to uncover any unfavourable effect of lidocaine on stability of (166)Ho-FHMA (ferrum hydroxide macroaggregate). METHODS: The radiopharmaceutical was investigated in bovine serum albumin (BSA) solutions (5, 10 mg/ml) at pH 6, 7 and 8. Furthermore, the tracer was incubated for 0, 2, 24, 48 and 120 hours in synovial fluid. In both series the influence of lidocaine-HCl 2% (500, 1000 microl) has been evaluated. RESULTS: In BSA test solutions, amount of lidocaine added [df(2), F=7.82, p-level: 0.00] and pH [df(2), F=7.82, p-level: 0.00] significantly influenced in vitro stability of (166)Ho labeled FHMA (n=72). This finding was confirmed in synovial fluid [df(2), F=3.82, p-level: 0.03] (n=60). CONCLUSION: In an experimental design mimicking normal and inflammatory conditions in the joint, addition of a few milliliters of lidocaine-HCl followed by a shift towards lower pH-values in synovial fluid may endanger stability of the carrier-tracer complex (166)Ho-FHMA and thereby enhance extra-articular leakage.

[Radiation doses deriving from patients treated with (166)Ho-ferric hydroxide]. / Strahlenexposition in der Umgebung von Patienten bei Radiosynoviorthese mit (166)Ho-Eisenhydroxid.

AIM: To estimate radiation doses deriving from patients treated with (166)Ho ferric hydroxide. METHODS: For radiation synoviorthesis about 900 +/- 100 MBq (166)Ho ferric hydroxide was injected into the knee joint of 16 patients. To estimate the radiation exposure of persons in the neighbourhood of the patients measurements of the dose rates were performed at 0.5 m, 1 m and 2 m distance of the treated joint 10 min after tracer injection. Measurements were carried out with and without radiation protection devices of the syringe. RESULTS: The initial values of the dose rate were 11.9 micro Sv/h at 0.5 m, 3.5 micro Sv/h at 1 m and 1 micro Sv/h at 2 m distance, respectively. The whole body doses were 2.9 micro Sv for the physician and 4.6 micro Sv for the technologist. The finger doses for the technologist and the physician were ranging from 65 to 111 micro Sv. After discharge at home other persons might receive 118 micro Sv. CONCLUSION: Our results, under very strict assumptions, clearly demonstrate that the calculated radiation exposure to medical and non medical personnel is well below the maximum annual dose limit. The use of any additional radiation protection device as syringe shielding does not significantly lower radiation exposure.

[Radiation exposure around patients after administration of 123-MIBG]. / Strahlenexposition im Umfeld von Patienten nach 123I-MIBG-Applikation.

AIM: Estimation of the radiation exposure to neighbouring patients, personnel and relatives deriving from patients undergoing 123I-MIBG scintigraphy. METHODS: For scintigraphic studies, 16 patients with suspected pheocromocytoma were injected with 340 +/- 30 MBq 123I-MIBG. Dose rates were measured at a distance of 0.5 m, 1 m, and 2 m after 10 min, 3 h, 21 h, 45 h, and 68 h using three calibrated portable radiation detectors. The emasured values were background corrected. RESULTS: Ten minutes after injection the dose rate was 10.5 microS/h at a distance of 0.5 m, 3.78 microS/h at 1 m, and 0.95 microS/h at 2 m. The effective half-life was estimated to 8.68 +/- 0.15 h. The maximum dose in a distance of 1 m for neighbouring patients was 46 microS/h, for personnel in a ward 27 microS/h, and to relatives in a distance of 2 m 12 microS/h. CONCLUSION: This study demonstrates that the calculated exposure to people around patients after 123I-MIBG injection is well below the maximum permissible annual dose limit of 1 mSv for not professionally exposed persons.

111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung.

UNLABELLED: Imaging with radiolabeled somatostatin (SST) analogs has recently been established for the localization of various human SST receptor (hsstr)-positive tumors, including neuroendocrine tumors, lymphomas, and non-small cell lung cancer (NSCLC). METHODS: 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN) scintigraphy (150 MBq; 7 nmol per patient) was performed on 47 patients (28 patients with primary tumors, 19 patients with lung metastases from other tumors) to evaluate the tumor binding in patients with histologically confirmed lung cancer. A group of 27 tumor patients without documented lung lesions served as the control group. Early and delayed planar and SPECT images were acquired. Whole-body scintigraphy was performed at 0.5, 4-6, 24, and 48 h after injection for tumor dose estimation. In addition, hsstr subtype expression and radioligand binding characteristics were studied in vitro using lung tumor samples (n = 15). RESULTS: 111In-DOTA-LAN indicated the primary lung tumor in 16 of 16 NSCLC patients. Lymph node metastases were visualized in 6 of 6 NSCLC patients, and bone metastases were seen in 3 of 3 NSCLC patients. 111In-DOTA-LAN scintigraphy indicated lung carcinoid in 5 of 5 patients and small cell lung cancer lesions in 6 of 6 patients. Multiple lung metastases were shown in all 6 patients with non-Hodgkin's lymphoma and in the 1 patient with Hodgkin's disease, 5 of 5 colorectal adenocarcinoma patients, 4 of 4 carcinoid patients, 2 of 2 neuroendocrine carcinoma (NEC) patients, and 1 of 1 angiosarcoma patient. Pulmonary tumor sites not indicated by CT or MRI were visualized in 6 of 47 tumor patients (i.e., 13%; lung metastases in 1 carcinoid patient and 1 NEC patient, lymph node metastases in 1 carcinoid patient and 2 NSCLC patients, bone metastases in 1 carcinoid patient). The estimated lung tumor dose ranged between 0.2 and 5 mGy/MBq. Focal lung uptake of 111In-DOTA-LAN was not observed in any of the 27 control patients. In vitro binding studies indicated high-affinity binding sites for 111In-DOTA-LAN in NSCLC samples (dissociation constants, 0.5 and 4 nmol/L) with predominant expression of hsstr4. CONCLUSION: 111In-DOTA-LAN yields high tumor binding for various human lung tumors. Consecutively, radiopeptide therapy may offer a potential new treatment alternative for some lung tumor patients.

New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy.

In vitro data have demonstrated a high amount of receptors for various hormones and peptides on malignant cells of neuroendocrine origin. Among these, binding sites for members of the SST-family (hSSTR1-5) are frequently found, and their expression has led to therapeutic and diagnostic attempts to specifically target these receptors. Receptor scintigraphy using radiolabeled peptide ligands has proven its effectiveness in clinical practice. In addition, initial results have indicated a clinical potential for receptor-targeted radiotherapy. Based on somatostatin (SST) receptor (R) recognition, the novel radiopharmaceuticals 111In/90Y-DOTA-lanreotide developed at the University of Vienna as well as 111In/90Y-DOTA-DPhe1-Tyr3-octreotide (NOVARTIS) both have provided promising data for diagnosis and treatment of hSSTR-positive tumors. SSTR scintigraphy using 111In-DTPA-DPhe1-octreotide has a high positive predictive value for the vast majority of neuroendocrine tumors and has gained its place in the diagnostic work-up as well as follow-up of patients. We have used 111In-DOTA-lanreotide scintigraphy in 166 patients since 1997 and have seen positive results in 93% of patients. In 42 patients with neuroendocrine tumors comparative data were obtained. As opposed to 111In-DTPA-DPhe1-octreotide and 111In-DOTA-DPhe1-Tyr3-octreotide, discrepancies in the scintigraphic results were seen in about one third of patients concerning both the tumor uptake as well as tumor lesion detection. Initial results both with 90Y-DOTA-lanreotide as well as 90Y-DOTA-DPhe1-Tyr3-octreotide has pointed out the clinical potential of radionuclide receptor-targeted radiotherapy. This new therapy could offer palliation and disease control at a reduced cost. The final peptide therapy strategy is most probably cheaper than conventional radiotherapies or prolonged chemotherapies. Overall, receptor-mediated radiotherapy with 90Y-DOTA-lanreotide/90Y-DOTA-DPhe1-Tyr3-octre otide might also be effective in patients refractory to conventional strategies.