PEPTIDE BASED TARGETED RADIONUCLIDE THERAPIES; SCIENCE BEHIND THE SUCCESS.

The radionuclide therapies for solid and liquid malignancies are emerging field nowadays. The targeted radionuclide therapies have been in use since 1945. In the past 20 years, due to advancement in the nanotechnology and targeting cell receptors; radionuclide therapies have emerged as a subspecialty in nuclear medicine. Through this article, we would like to briefly describe the evolution of peptide-based radionuclide therapies, with a little emphasis on their clinical applications. Key words: Peptide-based radiopharmaceuticals, radionuclide therapy, somatostatin-receptor-positive neuroendocrine tumou

A new microdispersed albumin derivative potentially useful for radio-guided surgery of occult breast cancer lesions

This paper describes a new nuclear imaging agent, 2-(4-isothiocyanatobenzyl) 121,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid of human albumin (HAC), potentially suitable for application in the Radio-guided Occult Lesion Localization (ROLL) of non-palpable mammalian cancerous lesions, as a tool to overtake the short radio-signal half-life of the technetium-99m based radiopharmaceutical currently used. This conjugate is a microsized powder aggregate, water-insoluble between pH 3 and 8.5, obtained by conjugating the protein with the macrocyclic chelating agent DOTA through a one-pot reaction in aqueous medium. The product has been fully characterized and is stable to the thermal conditions adopted for labeling; after radiolabeling with longer half-life radionuclides such as 177 Lu or 111 In, it has shown radiochemical purity (RCP) >90% and resulted stable when stored in saline or plasma for 6 days at 37 \ub0C. A \u3bcPET/CT study, performed in vivo on adult female rats, showed that the radioactivity of HAC labeled with 64 Cu remained located in the mammary glands for at least 40 h, without diffusion or drainage in healthy tissues or in the lymphatic circulation. This new imaging agent might make the ROLL procedure more accessible, safe and flexible, promoting a significant time and cost reduction of this intervention. Moreover, HAC might also be used in other radio-guided surgical procedures in oncology

Evaluation radiochemical purity of 177lu-labelled Rituximab conjugates using HPLC method

In the field of radiolabelled molecules, Rituximab appear as promising molecules for radiopharmaceutical design, because it can target specifically to antigensin non-Hodgkin lymphoma. In our project, Rituximab was conjugated with DTPA-, DOTA- and 1B4Mand prepared in a form of freeze dried kit formulation and labelled with 177Lu used was 565 MBq (in 5 µL) per kit. The reaction mixture was incubated at 380C for 1 hour. The radiochemical purity of the labeled conjugates was determined using SE-HPLC, Column BioSep-SEC-s3000 (300 x7.5 mm; Phenomenex), with flow rate 1ml/min, isocratic elution – eluent 0.1 M phosphate buffer pH 5.8, UV detection at 220 and 280 nm, analysis time ca. 20 min, sample volume: 20μl. To around 10 μl of radiolabelled conjugate 10 μl of 10 mM DTPA solution was added in order to bind non-reacted 177Lu. HPLC analysis was performed 5 min after DTPA addition using UV detection at 220 nm, 280 nm and radiometric detection. 177Lu-Rituximab radioimunoconjugates with high radiolabelling yield and average of radiochemical purity (above 94.7%) and specific activity up to 1.5GBq/mg was obtained. With the obtained results we can conclude that 177Lu- Rituximab radioimunoconjugates can be used for development of the predclinical studies in experimental animal model. Keywords: HPLC, 177Lu-Ab-DTPA, 77Lu-Ab-1B4M, 177Lu-Ab-DOT

Eleven-year experience with the avidin-biotin pretargeting system in glioblastoma: Toxicity, efficacy and survival

Background: The 3-step avidin-biotin pretargeting approach is applied in patients with recurrent glioblastoma (GBM), using biotinylated anti-tenascin monoclonal antibody as the first step of pretargeting followed by avidin and 90Ybiotin. Methods: The present study reviews objective response and overall survival rates in 502 glioblastoma patients treated with 3-step radioimmunotherapy in our institute from December 1994 to December 2005. Patients underwent standard treatment before receiving Pretargeted Antibody-Guided Radionuclide Therapy with 90Y-biotin (PAGRIT ®). Results: Of the 502 patients, 272 (54%) were evaluable for response and 375 (75%) for overall survival. 174 patients (64%) continued to progress after PAGRIT ®, 77 (28%) obtained disease stabilization, and 21 (8%) showed objective tumor regression. Survival of the 375 evaluable patients was 98.4% at 6 months, 79.2% at 12 months, 51.7% at 18 months, and 30.7% at 24 months after the first cycle of PAGRIT ®. All 375 received 3-step PAGRIT ® at recurrence of GBM. The median survival time from diagnosis was 19 months. Conclusion: The results from this retrospective analysis suggest that 90Y-biotin PAGRIT ® interferes with the progression of glioblastoma, prolonging survival in a larger number of patients. Our analysis forms the basis for further prospective trials, where radioimmunotherapy, which is known to be more effective in minimal residual disease, could be offered immediately after surgery. © Grana et al.; Licensee Bentham Open

Radiopharmaceuticals for radiation synovectomy: evaluation of two yttrium-90 particulate agents

Radiation synovectomy, a noninvasive therapeutic alternative to surgical synovectomy, has not gained widespread acceptance in the United States because of the lack of a suitable radiopharmaceutical. Two new radioactive particles, [90Y]Ca oxalate and [90Y]ferric hydroxide macroaggregates (FHMA), were developed in our laboratory and evaluated for size, stability, and joint leakage. More than 90% of the [90Y]Ca oxalate particles were in the optimal size range of 1-10 microns, and the unbound activity in serum and synovial fluid was 3.7% to 5.0%. Following injection in rabbit knees, leakage of [90Y]Ca oxalate was 5 +/- 2%, with localization primarily in the bone and virtually no uptake by the lymph nodes or liver. Yttrium-90 FHMA particles were larger (95% greater than 10 microns), and at least on a microscopic level, appeared to distribute homogeneously over the articular surface. Leakage of [90Y]FHMA was initially less but eventually slightly exceeded that of [90Y]Ca oxalate. Nevertheless, both radiopharmaceuticals can provide a satisfactory therapeutic dose to the knee with less than half the leakage and a marked reduction in absorbed dose to nontarget tissues compared to previously tested agents. Ease of preparation, physical characteristics of the 90Y beta ray, and apparent lack of substantial leakage from the joint make these agents extremely attractive for clinical evaluation in rheumatoid arthritis patients who are unresponsive to medical therapy

177Lu specific activity influence over DOTATATE radiolabeling: experimental data

[No abstract available

177Lu specific activity influence over DOTATATE radiolabeling: experimental data

[No abstract available