Current Radiopharmaceuticals - Volume 7, Issue 2, 2014

Alterations of the cardiac autonomic nervous system play an important role in the pathway of many heart diseases. Nuclear imaging tools have been demonstrated to be useful for global and regional assessment of myocardial innervation. We used 11C-meta-hydroxy-ephedrine (11C-mHED), a catecholamine analogue, as a radiotracer usable with a PET/CT scanner to study the cardiac sympathetic system. After a fast and automatic synthesis of mHED and its labeling with 11C, we acquired cardiac images by using a PET/ CT scanner. In this paper we present our preliminary results showing the radiotracer bio-distribution in humans 10 minutes post injection. The present study assesses the feasibility of PET/CT with the radiolabeled catecholamine analogue (11C-mHED) in order to determine sympathetic innervation in the human heart.

We described herein a simple and efficient microwave assisted synthesis of HYNIC analogues. Two different activated esters of HYNIC, the hydrazine protected with a trifluoroacetyl group (5) and the free hydrazine (6) were conjugated to the monoclonal antibody Nimotuzumab. Technetium-99m radiolabeling of Nimotuzumab was achieved with high efficiency using 5 and 6 derivates. The NHS-HYNIC-Tfa derivate allowed better labeling yields during longer times of preservation of the conjugated antibody.

The main purpose of this study was to evaluate Gd-DTPA kinetics for the differential diagnosis between malignant and benign breast lesions. As a secondary aim, Gd-DTPA kinetics in malignant lesions was tested for predicting axillary lymph nodes involvement. Eighty-eight patients who underwent MRI for suspected breast tumor were selected from our database. All patients underwent the same acquisition protocol consisting of pre-contrast and dynamic contrastenhanced MRI. For all of them clinical and histopathological data were available. MR studies were performed on the same 1.5T scanner with a standard dedicated breast coil. Pre- and post-contrast dynamic images were used to calculate R1, R2 relaxation rates and proton density maps. The maximum influx rate (MIR) as well as the corresponding time (TMIR) were derived using R1 relaxation rate maps and relative changes as a function of time. Histopatological analysis led to the diagnosis of 46 breast carcinomas and 42 benign lesions. All breast carcinomas and 24 out of 42 benign lesions showed contrast-enhancement. The mean MIR was 0.75±0.14 (SD) sec-2 in malignant tumors and 0.53±0.14 (SD) sec-2 in contrast-enhancing benign breast lesions (p<0.0001). The TMIR was 1.40±0.43 min and 3.01±1.92 min (mean±SD) in enhancing malignant and benign lesions, respectively (p<0.0001). In malignant tumors, TMIR was not significantly different in node negative and node positive carcinomas whereas MIR was significantly lower in node negative carcinomas (0.67±0.11 versus 0.83±0.12 respectively, p<0.0001). Our findings suggest that quantitative assessment of Gd-DTPA kinetics may be an additional tool characterized for enhancing breast lesions and for predicting axillary lymph nodes involvement in malignant breast carcinoma.

The dopamine D2 receptor radiotracer [11C]Raclopride is used extensively in clinical and preclinical imaging. Currently, a wide range of methods to produce [11C]Raclopride have been developed using traditional vessel reactions as well as cartridge or captive solvent. This work reports the optimisation of the production of [11C]Raclopride using a Synthra GPextent, comparing various methods. With optimised conditions, we were able to obtain 4±2% (ndc) yield of [11C]Raclopride (100 GBq [11C]CO2, n = 42) in 25 min. The radiochemical purity was >95% with specific activities of 135±41 MBq/nmol at end of synthesis.

When an intense intestinal FDG accumulation occurs, especially if focal, it can be referred to either physiological intestinal activity or bowel disease, thus leading to a radical change in patient’s prognosis. Within a year, we recommended a colonoscopy to 103 of 7365 patients who were subjected to a total body FDG PET/CT. In a case-series study, we re-evaluated the patients and their lesions if already investigated with colonoscopy and biopsy. Only 18 patients were included in our study, but in none of them biopsy was negative and 3 adenocarcinomas, 8 adenomas, 5 inflammatory patterns, 1 hyperplastic polyp and 1 eosinophilic infiltrate were diagnosed. In 16 patients, no suspicion was present and diagnosis was absolutely incidental. Besides, among the three major groups (adenocarcinomas, adenomas and phlogosis), SUVmax values were significantly different. Adenocarcinomas are linked with high SUVmax values (ranging from 8.3 to 20.2) and large size (ranging from 26 to 43 mm). PET/CT sensitivity is low in detecting adenomas, being 71.4% if they are larger than 6 mm and 50% if SUVmax is lower than 4.9. SUVmax values in inflammatory lesions can range from 5.7 to 12. Colorectal cancer is still the second leading cause of cancer death, for this reason in many countries screening programs have been approved and colonoscopy is considered the golden standard. PET/CT cannot be considered as a screening test, but if it incidentally reveals intestinal abnormalities, this data cannot be underestimated and colonoscopy is highly recommended.

Dendrimers are branched nanomolecules, with a three dimensional structure, very low polydispersity and high functionality. Poly(amidoamine) (PAMAM) dendrimers are the most investigated class of dendrimers. In this study, PAMAM G4 dendrimer conjugated with HYNIC (hydrazinonicotinamide), an efficient bifunctional chelator, was characterized. Structure of the derivatized dendrimer was confirmed by 1H-NMR and 13C-NMR spectra and MALDI-TOF mass spectrometry. HYNIC-dendrimer was labeled with technetium-99m testing three different co-ligands (tricine, nicotinic acid and ethylenediaminodiacetic acid). The radiolabeled complexes were characterized by reverse phase HPLC, as well as their stabilities. Radiolabeling yield was about 99% with all co-ligands and complexes were found stable for 24 h. Biodistribution studies were performed administrating tricine-99Tc-HYNIC-dendrimer, nicotinic acid-99Tc-HYNICdendrimer and EDDA-99Tc-HYNIC-dendrimer to normal mice; results showed blood clearance with hepatic and renal depuration in all cases. In this sense, labeling of PAMAM G4 dendrimer with technetium-99m using HYNIC could be obtained in high yield in a simple method and with high specific activity.

Proline and hydroxyproline represent major constituents of mammalian structural proteins, especially of collagen. An efficient radiosynthesis of the 18F-labeled proline derivatives cis-/trans-4-[18F]fluoro-L-proline was developed two decades ago with the aim to investigate various diseases with altered collagen synthesis using Positron-Emission- Tomography (PET). A number of studies have explored cis-4-[18F]fluoro-L-proline uptake in various pathologies associated with increased collagen formation and in neoplastic lesions, but so far the results have not been very promising. Trans-4-[18F]fluoro-L-proline has not yet been investigated in detail, however the compound exhibits considerable differences in metabolic behavior and biodistribution compared with its cis-enantiomer. In recent years, the D-isomers of cis- /trans-4-[18F]fluoro-proline have been considered as PET tracers as well, and it was observed that both exhibit a preferred uptake into the brain compared with their L-isomers. Surprisingly, a high uptake of cis-4-[18F]fluoro-D-proline was found in brain areas exhibiting secondary neurodegeneration as well as in areas of radionecrosis after treatment of brain tumors. In this article, the present knowledge on the biological and physiological properties of cis-/trans-4-[18F]fluoro-D/L-proline and the results in various pathologies are reviewed, including some previously unpublished results from our laboratory.

Medullary thyroid cancer (MTC) is considered as a rare thyroid cancer. Surgical approaches such as, total thyroidectomy and bilateral lymph node dissection, represent the first-line treatment. Persistent or increasing serum levels of tumor markers, such as CEA and calcitonin, imply residual or recurrent disease. An early and precise detection of recurrence is very important for guiding appropriate treatment. Recent developments in positron emission tomography (PET) imaging with different radiopharmaceuticals targeting specific hallmark of MTC, such as 18F-DOPA and 18F-FDG, have offered increased sensitivity for identifying recurrences. Moreover, the ability of conventional scintigraphic imaging to guide the surgical approach can be useful for the treatment of MTC recurrent patients. In the present work, we reported two cases of patients with recurrent MTC sending to surgical treatment guided by “nuclear medicine approaches”.

To study the comparative effects of beta radiation emitted from Na131I with equivalent dose of 60Co γ- radiation across a range of tumor types and underlying mechanism of cytotoxicity. Different tumor cell lines of various tissue origin viz. Raji, U937, A431 and MCF-7 were irradiated with beta radiation emitted from Na131I and equivalent dose of 60Co γ- radiation (0.4 Gy). Cellular toxicity and apoptosis study were carried out in four cell lines and the effects were compared. Gene expression studies of P21, RAD51 and BAX genes were analyzed by q-PCR after β- and γ-irradiation. Cell viability (trypan blue assay) and apoptosis (DNA fragmentation and cleavage of PARP assays) studies for both types of radiation showed that among the four cell lines, A431 is most radio-resistant while MCF-7 and U937 are moderately radiation resistant and Raji cells showed maximum radiosensitivity. However, irradiation of cells with beta radiation from I-131 resulted in enhanced toxicity and apoptosis in tumor cells compared to equivalent dose of γ- rays. Gene expression studies in Raji cells showed difference in magnitude and kinetics of RAD51 and P21 expression after β- and γ-irradiation. Our results showed higher efficacy of beta radiation in induction of tumor cell cytotoxicity and apoptosis compared to an equivalent dose of γ-radiation, which may be associated with differential DNA damage and subsequent repair kinetics in tumor cells after these radiations.

Infections by Candida spp and Aspergillus spp are the most common causes of invasive fungal infections. The main diagnostic methods are blood culture, and antigen-based techniques, but they are still suboptimal, leading to delays in the initiation of therapies and resulting in high mortality rates despite the availability of several new antifungal agents. The aim of this work was the development, synthesis and evaluation of a potential radiopharmaceutical enable the rapid and accurate diagnosis by scintigraphic images of fungal infection using caspofungin, a lipopeptide, radiolabelled with 99Tc. Caspofungin was radiolabeled with 99Tc-tricarbonyl precursor. The complex was assessed for in vitro stability, lipophilicity, plasma protein binding and plasma stability. Biological evaluation was conducted in four groups of CD1 female mice. G1 healthy animals, G2 was induced sterile inflammation with turpentine oil. G3 and G4 were infected with Candida albicans and Aspergillus Niger. Scintigraphicimages were acquired before sacrifice. The Caspofungin – tricarbonyl complex was obtained with RCP higher than 95%, it was stable in labeling milieu for at least 20 hours, and in plasma for 4 hours. Challenge with competitive agents showed no ligand exchange during 200 min. The product was well tolerated by mice and showed mainly hepatobiliar excretion. Lesion uptake was markedly higher in infected tissues than in sterile inflammation. Scintigraphic images clearly distinguished inflammation from infection. The high RCP yields and in vitro stability, the targeted biodistribution profile and good T/NT ratios, outlines this complex as a potential agent for rapid and specific diagnosis of infections caused by pathogenic yeasts.