This work describes the production of very high specific activity 66/68Ga from natZn(p,n) and 66Zn(p,n) using proton irradiations between 7 and 16 MeV, with emphasis on 66Ga for use with common bifunctional chelates. Principle radiometallic impurities are 65Zn from (p,x) and 67Ga from (p,n). Separation of radiogallium from target material is accomplished with cation exchange chromatography in hydrochloric acid solution. Efficient recycling of Zn target material is possible using electrodeposition of Zn from its chloride form, but these measures are not necessary to achieve high specific activity or near-quantitiative radiolabeling yields from natural targets. Inductively coupled plasma mass spectroscopy (ICP-MS) measures less than 2 ppb non-radioactive gallium in the final product, and the reactivity of 66Ga with common bifunctional chelates, decay corrected to the end of irradiation, is 740 GBq/μmol (20 Ci/μmol) using natural zinc as a target material. Recycling enriched 66Zn targets increased the reactivity of 66Ga with common bifunctional chelates.

Background:Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as 99mTc-LD distribution in MPM lesions after chemotherapy administration.Methods:A total of 38 patients with non-resectable MPM received LD 40 mg m−2 and cisplatin 60 mg m−2 every 21 days. Gamma camera images of 99mTc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028).Results:In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4–5.9 months), and median overall survival (OS) was 19.6 months (15.2–37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001).Conclusion:The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. 99mTc-LD showed higher levels of tumour uptake as compared with surrounding tissues.

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Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for α v β 3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from 68 Ga-DOTA-E-[c(RGDfK)] 2 using whole-body PET scans in humans. Methods: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/ EXM software was applied to calculate human radiation doses using the reference adult model. Results: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively. Conclusion: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with 68 Ga and 18 F. Therefore, 68 Ga-DOTA-E-[c(RGDfK)] 2 can safely be used for imaging integrin α V β 3 expression. The last few years have witnessed the development of a virtual revolution in PET molecular imaging, and radiolabeled receptor-binding peptides are emerging as powerful tools for imaging and therapy applications of tumors expressing peptide binding receptors (1-3). Somatostatin analogs have been in use the longest, have led to the accumulation of a vast amount of data, and have proven useful for the management of patients with neuroendocrine tumors (4-8). Several other peptide receptorbinding compounds have been synthesized within the past few years and are currently in various research stages-in vitro, in vivo, and preclinical studies-but have not yet been approved for clinical use (9-11). These new and rapidly expanding peptide-based radiopharmaceuticals deserve close attention.It has been shown that peptides based on the RGD amino acid sequence have a high affinity and selectivity for a V b 3 integrin receptors (12). The a V b 3 integrins are transmembrane proteins that are preferentially expressed on proliferating endothelial cells but absent from quiescent endothelial cells (13). Integrins are overexpressed on newly formed blood vessels of actively growing tumors and are therefore potential targets for receptor-mediated tumor imaging and therapy when labeled with the proper radionuclide. Angiogenesis, the formation of n...

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The aim of this research was to evaluate the biological behavior in Wistar rats of a multifunctional system of gold nanoparticles (AuNP) conjugated to 99m Tc-HYNIC-GGC and mannose for sentinel lymph node (SLN) specific detection. The radiolabeled nanoconjugate, characterized by TEM and UV-vis, vibrational, XPS and Fluorescence spectroscopic analyses, was administered in rats (footpad) and the radioactivity levels in the popliteal and inguinal lymph nodes determined at different times from 30 min to 24 h. Results showed that 21% of the injected radio-AuNP-mannose was retained in the first lymph node (popliteal) during 24 h. 99m Tc-HYNIC-GGC-AuNP-Mannose is a potential target-specific tracer for SLN detection in breast cancer patients.