Radiolabelling of engineered nanoparticles for in vitro and in vivo tracing applications using cyclotron accelerators.

We present in this article an outline of some cyclotron-based irradiation techniques that can be used to directly radiolabel industrially manufactured nanoparticles, as well as two techniques for synthesis of labelled nanoparticles using cyclotron-generated radioactive precursor materials. These radiolabelled nanoparticles are suitable for a range of different in vitro and in vivo tracing studies of relevance to the field of nanotoxicology. A basic overview is given of the relevant physics of nuclear reactions regarding both ion-beam and neutron production of radioisotopes. The various issues that determine the practicality and usefulness of the different methods are discussed, including radioisotope yield, nuclear reaction kinetics, radiation and thermal damage, and radiolabel stability. Experimental details are presented regarding several techniques applied in our laboratories, including direct light-ion activation of dry nanoparticle samples, neutron activation of nanoparticles and suspensions using an ion-beam driven activator, spark-ignition generation of nanoparticle aerosols using activated electrode materials, and radiochemical synthesis of nanoparticles using cyclotron-produced isotopes. The application of these techniques is illustrated through short descriptions of some selected results thus far achieved. It is shown that these cyclotron-based methods offer a very useful range of options for nanoparticle radiolabelling despite some experimental difficulties associated with their application. For direct nanoparticle radiolabelling, if care is taken in choosing the experimental conditions applied, useful activity levels can be achieved in a wide range of nanoparticle types, without causing substantial thermal or radiation damage to the nanoparticle structure. Nanoparticle synthesis using radioactive precursors presents a different set of issues and offers a complementary and equally valid approach when laboratory generation of the nanoparticles is acceptable for the proposed studies, and where an appropriate radiolabel can be incorporated into the nanoparticles during synthesis.

Clinical use of an imaging probe in breast cancer surgery.

AIMS: Portable cameras allow easy transfer of the detector, and thus of radioisotope imaging, to the operating room. In this paper we describe our preliminary experience in radionuclide imaging of breast cancer with a 22.8 x 22.8 mm(2) field-of-view minicamera called "Imaging Probe" (IP). METHODS: Breast cancer detection by IP was performed to guide biopsy, in particular open biopsy, or help fine-needle or core-needle positioning when the main guidance method was ultrasonography or digital radiography. 99mTc Sestamibi (MIBI) was injected 1 h before imaging and biopsy to 14 patients with suspected or known breast cancer. Scintigraphic images were acquired before and after biopsy in each patient. The surgeon was allowed to take into account scintigraphic images as well as previously performed mammograms and ultrasonography. RESULTS: High-resolution IP images were able to guide biopsy toward cancer or toward washout zones of cancer which are thought to be chemoresistant in seven patients out of 10. Four patients in whom IP and MIBI were unable to guide biopsy were found not to have cancer. CONCLUSIONS: Our study confirms the ability of IP to guide breast biopsy even when our minicamera has to be handled manually by trained physicians during surgery.

New localization technique for breast cancer biopsy: mammotome guidance with imaging probe.

AIMS AND BACKGROUND: The "Imaging Probe" (IP) is a small, portable, high-resolution gamma camera to be used in radioguided surgery. The present work discusses a special prototype designed for guiding biopsies. The IP was mounted to a Fischer digital X-ray stereotactic core biopsy system in such a way that biopsy could be guided simultaneously by X-ray stereotaxis and 99mTc-Sestamibi (MIBI) images from IP. METHODS: The IP field of view was 22.8 x 22.8 mm(2), with a spatial resolution of approx. 2.5 mm. We used off-line software for image fusion on a dedicated Pentium III portable PC. It was matched with a Fischer digital X-ray stereotactic biopsy system dedicated to direct the mammotome towards breast opacities. The operator was allowed to slightly correct the direction of the mammotome needle taking into account stereotactic X-ray, scintigraphic and fused images. Biopsy samples were counted by IP before they were sent to the pathologist. RESULTS: High-resolution IP scintigraphy showed substantial, though not exact, matching between MIBI hot spots and X-ray opacities. More than one hot spot was detected even in the smallest (0.6 cm) lesion. Post-biopsy scintigraphy showed absence of significant hot spots in two patients, whereas in the third patient one of the three hot spots was still partially present. All lesions showed cancer on histological examination. CONCLUSIONS: Measurement of radioactivity in biopsy specimens confirmed the heterogeneous distribution of radioactivity within cancers that IP had detected before biopsy.

Radioguided biopsy of osteoid osteoma: usefulness of imaging probe.

AIMS AND BACKGROUND: When removal of osteoid osteoma is performed with open biopsy, the surgeon can be guided by radioactivity of 99mTc-MDP (methylene D- phosphonate) acquired by a probe. MATERIAL AND METHODS: We compared the performance of a commercially available ZnCdTe probe (Neoprobe 2000) and a one-square-inch-field-of-view imaging probe (IP) on two patients undergoing open biopsy for osteoid osteoma. Triphasic bone scintigraphy was performed before operation and Neoprobe as well as IP were used in the operating room by two nuclear physicians. When the surgeon asked for guidance, each nuclear physician had to indicate a precise direction. RESULTS: The surgeon asked for guidance once in the first operation, on a patient with osteoid osteoma of the femur, and four times in the second operation, for osteoid osteoma of the acetabulum. The indications provided by IP were correct 5/5 times, whereas the commercial probe was correct 3/5 times. Both devices were able to assess the surgical radicality. After biopsy, bone samples were divided into high-count and low-count samples. Pathological examination confirmed the presence of osteoid osteoma in high-count samples. CONCLUSIONS: IP has already been used to guide biopsy, but only in breast disease. The present work confirmed its good performance also in orthopedics as a portable mini gamma camera that can be used in the operating room.

Sentinel node detection with imaging probe.

A once-square-inch-field-of-view mini gamma camera, whose first prototype was built by us in 1998 and given the name imaging probe (IP), was initially employed in sentinel lymph node (SLN) detection. This is probably the best way of learning how to use it. In the present work IP was used for SLN localization by a medical team that, after having been trained by the group of nuclear physicians of "La Sapienza" University who designed and first used the detector, used IP at their own hospital to 1) acquire experience for future use during surgery (a cooperative project on IP-radioguided orthopedic surgery is ongoing) and 2) start multicenter trials with IP. The SLN was identified and localized with IP and a non-imaging probe, Neoprobe 2000, in six patients with breast cancer who underwent lymphoscintigraphy for SLN biopsy. The operators who used Neoprobe and IP were blinded to each other's findings and to the results obtained with the large-field-of-view Anger camera that was used for lymphoscintigraphy. The Anger camera, IP and Neoprobe detected seven SLNs in six patients. The mean detection time was 2 mins 6 s (standard deviation (SD) 26 s) with IP, and 2 mins 18 s (SD 47 s) with Neoprobe 2000. The SLN that was most difficult to find was detected in 2 mins 56 s with IP and 3 mins 45 s with Neoprobe. The operators' subjective impression of having detected the SLN was "absolutely sure" for 7/7 nodes with IP and "absolutely sure" for 5/7 nodes with Neoprobe.

Monte Carlo design for a new neutron collimator at the ENEA Casaccia TRIGA reactor.

The TRIGA RC-1 1MW reactor operating at ENEA Casaccia Center is currently being developed as a second neutron imaging facility that shall be devoted to computed tomography as well as neutron tomography. In order to reduce the gamma-ray content in the neutron beam, the reactor tangential piercing channel was selected. A set of Monte Carlo simulation was used to design the neutron collimator, to determine the preliminary choice of the materials to be employed in the collimator design.

Brachytherapy: state of the art and possible improvements.

Cancer often remains an incurable disease, despite significant progresses in diagnosis and treatment that have been made. Specifically, the use of nuclear medicine in oncology is greatly contributing to both imaging and therapy aspects. Targeted therapies are a major field of interest since it increases efficiency and reduces side effects. Brachytherapy is among the most valuable of recent developments for treating localized tumours resulting in improvements in improved quality of life. This is primarily because it irradiates cancerous cells most exclusively while barely effecting healthy tissue. The use of radiochemicals implies specific management for production, transport and handling that have limited the development of this technique. This review article describes brachytherapy and their latest developments. Furthermore, alternative activation methods for the production of radioisotopes and a novel delivery system for targeted multi-therapy by using PLA-ferrite nanospheres are described.