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So far, numerous molecules and biomolecules have been evaluated for tumor targeting purposes for radionuclide-based imaging and therapy modalities. Due to the high affinity and specificity against tumor antigens, monoclonal antibodies are appropriate candidates for tumor targeting. However, their large size prevents their comprehensive application in radionuclide-based tumor imaging or therapy, since it leads to their low tumor penetration, low blood clearance, and thus inappropriate tumor-to-background ratio. Nowadays, the variable domain of heavy-chain antibodies from the Camelidae family, known as nanobodies (Nbs), turn into exciting candidates for medical research. Considering several innate advantages of these new tumor-targeting agents, including excellent affinity and specificity toward antigen, high solubility, high stability, fast washout from blood, convenient production, ease of selection, and low immunogenicity, it assumes that they may overcome generic problems of monoclonal antibodies, their fragments, and other vectors used for tumor imaging/therapy. After three decades of Nbs discovery, the increasing number of their preclinical and clinical investigations, which have led to outstanding results, confirm their application for tumor targeting purposes. This review describes Nbs characteristics, the diagnostic and therapeutic application of their radioconjugates, and their recent advances.

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Diabetic foot infection is a preventable complication of diabetes mellitus. It is an essential component of diabetic foot disease, which is characterised by a triad of neuropathy, ischaemia and infection. These factors may lead to foot ulceration, sepsis and amputation resulting in increased morbidity and poor quality of life. Confirming or excluding infection can be difficult especially when routine laboratory tests and plain radiographs are inconclusive. Early diagnosis and localization of diabetic foot infection is extremely important to institute timely, appropriate therapy. Structural imaging using computed tomography and magnetic resonance imaging all have individual applications towards the diagnostic workup of this condition but have their own limitations. Scintigraphic detection is based on physiochemical changes and hence provides a functional evaluation of bone pathology. We describe the evolution of functional nuclear medicine imaging including immunoscintigraphy in diabetic foot infection and highlight current applications of physiological 18-Fluoro-deoxyglucose positron emission tomography (18-FDG-PET) and computed tomography (18-FDG-PET/CT) in such patients. 18-FDG-PET/CT is a promising modality for imaging diabetic foot infection. Future studies will allow standardisation of technological details and options of 18-FDG-PET/CT interpretation in diabetic foot infection.

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This article discusses the current position of conventional radiography and MRI, the techniques recommended by the European League Against Rheumatism for use in imaging in axial spondyloarthritis (axSpA). Several challenges and areas of development regarding radiography and MRI in axSpA are considered. Also, a few interesting focus points for future research are noted. Besides the recommended techniques, this article discusses several nuclear imaging techniques and the usability of these techniques in daily practice.

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BACKGROUND: Surgical treatment of non-palpable breast lesions is controversial. At the European Institute of Oncology in Milan, Italy, Prof Umberto Veronesi introduced a new technique called the radioguided occult lesion localisation (ROLL) in 1996 to replace conventional methods and their disadvantages (Zurrida S, Galimberti V, and Monti S et al (1998) Radioguided localization of occult breast lesionsBreast7 11-13 https://doi.org/10.1016/S0960-9776(98)90044-3). Given the success experienced in that institution, the method became the technique of choice for the early diagnosis of breast cancer. In this paper, we will examine the technical aspects of ROLL and the results from a large series of patients treated in our private practice in Costa Rica. METHODS: We analysed the first 816 patients with different non-palpable breast lesions detected by ultrasound or mammography within our private practice in Costa Rica. In 774 patients, technetium 99m labelled with human serum albumin (7-10 MBq) in 0.2 ml of saline solution was injected into the lesion under mammographic or ultrasound guidance. The excisional biopsy was done by means of a gamma-probe and complete excision of the lesion was verified by X-ray on the specimen in lesions that were visible by mammography and ultrasound 4 months after surgery. In the remaining 42 patients, the localisation of the lesion was carried out by wire. RESULTS: The tracer was correctly positioned in the first attempt in 772/816 (94.6%) of cases and in the second attempt in two other cases. In 42/816 (5.1%) cases, the localisation of the lesion had to be performed with the traditional method. X-rays showed that the lesion was entirely removed in 770/772 (99.74%) of cases. CONCLUSION: The ROLL is a simple and excellent option for the removal of hidden breast lesions in clinical practice. It offers the advantage of making resections safer and with tumour-free margins, in addition to reducing the number of reinterventions. Since it makes it possible to specify to the pathologist the exact site where the lesion is located, we can guarantee a better diagnosis. The rate of success with the use of this technique corresponds to the available scientific data, so we conclude that it is a procedure that we can routinely perform in private practice in Costa Rica.

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BACKGROUND: Oncological pretargeting has been implemented and tested in several different ways in preclinical models and clinical trials over more than 30 years. Despite highly promising results, pretargeting has not achieved market approval even though it could be considered the ultimate theranostic, combining PET imaging with short-lived positron emitters and therapy with radionuclides emitting beta or alpha particles. RESULTS: We have reviewed the pretargeting approaches proposed over the years, discussing their suitability for imaging, particularly PET imaging, and therapy, as well as their limitations. The reviewed pretargeting modalities are the avidin-biotin system, bispecific anti-tumour x anti-hapten antibodies and bivalent haptens, antibody-oligonucleotide conjugates and radiolabelled complementary oligonucleotides, and approaches using click chemistry. Finally, we discuss recent developments, such as the use of small binding proteins for pretargeting that may offer new perspectives to cancer pretargeting. CONCLUSIONS: While pretargeting has shown promise and demonstrated preclinical and clinical proof of principle, full-scale clinical development programs are needed to translate pretargeting into a clinical reality that could ideally fit into current theranostic and precision medicine perspectives.

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Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed.

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AIM: To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer. METHODS: Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocarcinoma suspected of local recurrence and metastatic disease. The results were compared with conventional diagnostics. RESULTS: Immunoscintigraphic investigation was done in 53 patients. Tumor recurrence occurred in 38 patients, and was confirmed by other diagnostic modalities in 35. In 15 patients, immunoscintigraphic findings were negative, and confirmed in 14 with other diagnostic methods. Comparative analysis confirmed good correlation of immunoscintigraphic findings and the results of conventional diagnostics and the level of tumor marker carcinoembryonic antigen. Statistical analysis of parameters of radiopharmaceutical groups imacis, indimacis and oncoscint presented homogenous characteristics all of three radiopharmaceuticals. The analysis of immunoscintigraphic target focus was clearly improved using tomography. CONCLUSION: Immunoscintigraphy is highly specific and has a good predictive value in local recurrence of colorectal cancer.

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We evaluated the effectiveness of Tc-99m labeled antigranulocyte antibody immunoscintigraphy in differentiating the causes of vertebral compression fracture. This study involved 16 patients with vertebral compression fracture; 8 were due to trauma or osteoporosis, 3 were due to metastasis and 5 were due to tuberculous spondylitis. We retrospectively analyzed the location and the extent of decreased tracer uptake in tomographic images of Tc-99m labeled antigranulocyte antibody immunoscintigraphy. Eight patients had a 16 vertebral compression fractures due to trauma or osteoporosis , three patients had a 3 vertebral compression fractures due to metastasis and 5 patients had a 6 vertebral compression fractures due to tuberculous spondylitis. Sixteen vertebral compression fractures by trauma or osteoporosis showed a normal tracer uptake in pedicle, laminar and spinous process, but there was noted with 6 decreased uptake, 8 absence of tracer uptake and 2 normal tracer uptake in the vertebral body. Two vertebral compression fractures by metastasis showed the absence of uptake in vertebral body, pedicle, laminar and spinous process, and one showed an absence of vertebral body and spinous process. Six vertebral compression fractures by tuberculous spondylitis showed the absence of uptake in six compression fractures, the absence of pedicle in five compression fractures. We concluded Tc-99m labeled antigranulocyte antibody immunoscintigraphy may be helpful to differentiate the causes of vertebral compression fractures.

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