Mobile gamma cameras in breast cancer care - a review.

BACKGROUND: Currently, due to progress in detection and to extended screening, surgeons have to deal with increasing numbers of non-palpable lesions in breast cancer. These lesions can be treated by radio-guided surgery in the lumpectomy associated with sentinel lymph node (SLN) procedures. Thanks to advances in detector technology, mini gamma cameras are now available, that can perform real-time lymphoscintigraphy during surgery, or at bedside. AIM: In this article, we review the clinical literature on these dedicated cameras used in breast cancer surgery. The goal is to show how these cameras are used in breast cancer treatment and in SLN biopsy and what kind of benefits they offer. METHODS: We conducted our search on MEDLINE and EMBASE databases. We performed a comprehensive review to identify clinical studies or cases using mobile gamma cameras in breast cancer surgery. RESULTS: We collected 14 articles published between January 2000 and March 2012. We analysed the use of the mobile cameras and the obtained results. CONCLUSION: Mobile gamma cameras seem to be useful imaging tools either used pre-operatively or during surgery. They assist surgeons with accurate localization of SLNs and/or radio-labelled tumours, and in verification that all radioactive nodes have been excised.

[Place of hand-held gamma-cameras in breast cancer]. / Place des gamma-caméras portables en cancérologie mammaire.

Non-palpable breast cancers are more and more frequent. Their surgical management requires the excision of the tumor and sentinel lymph node (SLN) needing a technical preoperative organization combining preoperative identification of the tumor by wire guide and injection of a radioactive tracer for the identification of SLN. The implementation of this minimally invasive surgery is sometimes paradoxically complicated due to the presurgical organization requiring several medical teams. It is for this reason that hand-held gamma-cameras have been developed, used either preoperatively or during surgery to replace lymphoscintigraphy but also as a help to excision of the tumor after radioisotope injection. The objective of this study was to evaluate the interest of the main hand-held gamma-cameras used in breast cancer.

Development of a positron probe for localization and excision of brain tumours during surgery.

The survival outcome of patients suffering from gliomas is directly linked to the complete surgical resection of the tumour. To help the surgeons to delineate precisely the boundaries of the tumour, we developed an intraoperative positron probe with background noise rejection capability. The probe was designed to be directly coupled to the excision tool such that detection and removal of the radiolabelled tumours could be simultaneous. The device consists of two exchangeable detection heads composed of clear and plastic scintillating fibres. Each head is coupled to an optic fibre bundle that exports the scintillating light to a photodetection and processing electronic module placed outside the operative wound. The background rejection method is based on a real-time subtraction technique. The measured probe sensitivity for (18)F was 1.1 cps kBq(-1) ml(-1) for the small head and 3.4 cps kBq(-1) ml(-1) for the large head. The mean spatial resolution was 1.6 mm FWHM on the detector surface. The gamma-ray rejection efficiency measured by realistic brain phantom modelling of the surgical cavity was 99.4%. This phantom also demonstrated the ability of the probe to detect tumour discs as small as 5 mm in diameter (20 mg) for tumour-to-background ratios higher than 3:1 and with an acquisition time around 4 s at each scanning step. These results indicate that our detector could be a useful complement to existing techniques for the accurate excision of brain tumour tissue and more generally to improve the efficiency of radio-guided cancer surgery.

Radio-imaging for quantitative autoradiography in biology.

We present here an overview of new in vitro and ex vivo radio-imaging systems developed to overcome the limitations of films and emulsions currently used in histological autoradiography experiments. The shortcomings of films for quantitative studies are first introduced. Principles and performances of each family of imagers are discussed and illustrated in various biological contexts. Finally, perspectives of development including nonradioactive labeling techniques are briefly presented.

A new high resolution radioimager for the quantitative analysis of radiolabelled molecules in tissue section.

We present a high-speed, high-resolution imager of beta particles. It is devoted to be used in autoradiography experiments such as receptor binding or in situ hybridization experiments, either instead of, or in complement with autoradiographic film and emulsions. It allows the user to locate and perform quantitative analyses of (3H, 14C, 35S, 33P, 32P, 125I) labelled molecules with a 15 microm spatial resolution on a 0.9 x 1.3 cm2 sensitive area. Combining recent techniques (specific scintillator thin sheets and intensified charge-coupled device (CCD)) this imager offers a wide dynamic range and real-time acquisition.

Radioimagers as an alternative to film autoradiography for in situ quantitative analysis of 125I-ligand receptor binding and pharmacological studies.

Three radioimagers, the mu-imager, the beta-imager and the phosphorimager, were tested as alternatives to quantitative autoradiography on film, for receptor imaging and pharmacological in situ quantitative analysis. Two iodinated ligands 125I-interleukin-1 alpha and 125I-gonadotropin releasing hormone agonist were used for receptor characterization in mouse brain and pituitary sections. Due to the high number of the agonist receptors in rat pituitary gland, this tissue was used to compare measurements obtained from digital autoradiograms with classical gamma detector determination. This permits the evaluation of radioimager efficiency and absolute quantification. Radioimagers represent an improvement in terms of time of image acquisition. All the radioimagers are more sensitive than film for the detection of low levels of radioactivity. The spatial resolution provided by the mu-imager compares favourably with that obtained on film autoradiograms while digital autoradiograms from the phosphorimager and beta-imager did not show precise definition under our experimental conditions. Superimposition of histological structures from the stained sections with radiolabelled areas in the autoradiograms remains, at this time, the unique advantage of film. In conclusion, radioimagers represent an alternative to autoradiography on film or emulsion for in situ quantitative studies on tissue sections. They combine precise imaging for in situ binding studies with easy and direct access to counts in cpm. The improvement in radioimaging technology has, therefore, brought in situ analysis of iodinated ligand binding to the level of accuracy that is obtained with classical detectors of radioactivity.

A novel rat tyrosine hydroxylase mRNA species generated by alternative splicing.

Tyrosine hydroxylase (TH) catalyzes the first and rate-limiting step in the biosynthesis of catecholamines. Among the various mechanisms implicated in the regulation of TH activity, alternative splicing of TH primary transcript has been described as a characteristic of higher primates and Drosophila. We investigated whether there is such a regulatory mechanism in the rat. Reverse transcriptase-PCR experiments were performed with RNA from PC12 cells. A new TH mRNA species was evidenced, resulting from the use of an alternative donor site in exon 2. RNase protection assays and in situ hybridization experiments detected this mRNA species in the adrenal medulla but not in the main catecholaminergic nuclei of the CNS. The corresponding putative protein lacks 33 amino acids in the N-terminal regulatory domain. A recombinant protein was produced in E. coli. Its in vitro specific activity was similar to that of the previously identified TH protein.

HRRI: a high resolution radioimager for fast, direct quantification in in situ hybridization experiments.

We present a high-speed, high-resolution beta imager. It has been developed to be used in in situ hybridization experiments, either instead of or in complement with autoradiographic film and emulsions that are currently used for these experiments. It allows the user to locate and perform quantitative analyses of (3H-, 14C-, 35S-, 32P-, 125I-) labeled molecules with a 15-microns spatial resolution on a 1.2 cm2 area. We have combined recent techniques (specific scintillator thin sheets and intensified charge-coupled device [CCD]) so that this imager offers a wide dynamic range and real-time acquisition. Several biological applications will be discussed.

"In situ" characterization of GnRH receptors: use of two radioimagers and comparison with quantitative autoradiography.

New radioimagers, the HRRI (high resolution radioimager) and the Phosphorimager (phosphor screen : PS), apt to display more ample linear dose-response scale than radio-sensitive films, were tested in comparison with quantitative autoradiography (QA). GnRH receptor saturation experiments were achieved on tissue sections (rat pituitary, rat brain, human ovary) with a iodinate GnRH agonist (125I-[D-Ala6,Des-Gly10]-LH-RH Ethylamide) for determination of affinity constant (Kd). In rat pituitary, comparable results were obtained with the 3 methods (Kd: 0.4 to 0.6 nM). Discrepancies occurred in the hippocampus and in the granulosa cell layer of the preovulatory follicle, due to low resolutive (PS) or short linear dose-response (films) performances. In the hippocampus GnRH receptor affinity was under-estimated with PS (Kd: 2.3 vs 0.5 and 0.6 nM for QA and HRRI respectively). In the follicular granulosa cell layer it was over-estimated by QA (0.5 vs 50 nM for the HRRI), while PS did not allow resolution of this thin cell layer. In conclusion, the HRRI is a very powerful tool for the quantification of in situ radioligand binding (binding sites study and in situ hybridization) in very discrete areas.

SOFI: a bidimensional detector for fast direct on-line quantification of beta particles on blots.

We present a high-speed, high-resolution beta imager developed to replace autoradiographic films currently used in molecular biology experiments. It allows the user to locate and make quantitative analyses of 32P-labeled molecules on a 25.6 x 25.6-cm flat surface. Combining new techniques--scintillating optical fibers and multianode photomultipliers--this fast imager offers several advantages when compared with recent gas detectors and flexibility for further improvements. Several biological applications will be discussed.