Hypoxia promotes angiogenesis, which is crucial for tumor growth, and induces malignant progression and increases the therapeutic resistance. Positron emission tomography (PET) enables the detection of the hypoxic regions in tumors using 2-nitroimidazole-based radiopharmaceuticals. We describe here a physicochemical study of the Sc(DO3AM-NI) complex, which indicates: (a) relatively slow formation of the Sc(DO3AM-NI) chelate in acidic solution; (b) lower thermodynamic stability than the reference Sc(DOTA); (c) however, it is substantially more inert and consequently can be regarded as an excellent Sc-binder system. In addition, we report a comparison of ⁴⁴Sc-labeled DO3AM-NI with its known ⁶⁸Ga-labeled analog as a hypoxia PET probe. The in vivo and ex vivo biodistributions of ⁴⁴Sc- and ⁶⁸Ga-labeled DO3AM-NI in healthy and KB tumor-bearing SCID mice were examined 90 and 240 min after intravenous injection. No significant difference was found between the accumulation of ⁴⁴Sc- and ⁶⁸Ga-labeled DO3AM-NI in KB tumors. However, a significantly higher accumulation of [⁶⁸Ga]Ga(DO3AM-NI) was found in liver, spleen, kidney, intestine, lung, heart and brain than for [⁴⁴Sc]Sc(DO3AM-NI), leading to a lower tumor/background ratio. The tumor-to-muscle (T/M) ratio of [⁴⁴Sc]Sc(DO3AM-NI) was approximately 10–15-fold higher than that of [⁶⁸Ga]Ga(DO3AM-NI) at all time points. Thus, [⁴⁴Sc]Sc(DO3AM-NI) allows the visualization of KB tumors with higher resolution, making it a promising hypoxia-specific PET radiotracer.

Tumor hypoxia induces angiogenesis, which is required for tumor cell survival. The aminopeptidase N receptor (APN/CD13) is an excellent marker of angiogenesis since it is overexpressed in angiogenic blood vessels and in tumor cells. Asparagine-glycine-arginine (NGR) peptide analogs bind selectively to the APN/CD13 recepto, therefore, they are important vector molecules in the development of a PET radiotracer which is capable of detecting APN-rich tumors. To investigate the effect of glycosylation and pegylation on in-vivo efficacy of an NGR-based radiotracer, two ⁶⁸Ga-labeled radioglycopeptides were synthesized. A lactosamine derivative was applied to glycosylation of the NGR derivative and PEG₄ moiety was used for pegylation. The receptor targeting potential and biodistribution of the radiopeptides were evaluated with in vivo PET imaging studies and ex vivo tissue distribution studies using B16-F10 melanoma tumor-bearing mice. According to these studies, all synthesized radiopeptides were capable of detecting APN expression in B16-F10 melanoma tumor. In addition, lower hepatic uptake, higher tumor-to background (T/M) ratio and prolonged circulation time were observed for the novel [⁶⁸Ga]-10 radiotracer due to pegylation and glycosylation, resulting in more contrasting PET imaging. These in vivo PET imaging results correlated well with the ex vivo tissue distribution data.

Radiolabeled peptides possessing an Arg-Gly-Asp (RGD) motif are widely used radiopharmaceuticals for PET imaging of tumor angiogenesis due to their high affinity and selectivity to α_vβ₃ integrin. This receptor is overexpressed in tumor and tumor endothelial cells in the case of numerous cancer cell lines, therefore, it is an excellent biomarker for cancer diagnosis. The galectin-3 protein is also highly expressed in tumor cells and N-acetyllactosamine is a well-established ligand of this receptor. We have developed a synthetic method to prepare a lactosamine-containing radiotracer, namely ⁶⁸Ga-NODAGA-LacN-E[c(RGDfK)]₂, for cancer diagnosis. First, a lactosamine derivative with azido-propyl aglycone was synthetized. Then, NODAGA-NHS was attached to the amino group of this lactosamine derivative. The obtained compound was conjugated to an E[c(RGDfK)]₂ peptide with a strain-promoted click reaction. We have accomplished the radiolabeling of the synthetized NODAGA-LacN-E[c(RGDfK)]₂ precursor with a positron-emitting ⁶⁸Ga isotope (radiochemical yield of >95%). The purification of the labeled compound with solid-phase extraction resulted in a radiochemical purity of >99%. Subsequently, the octanol–water partition coefficient (log P) of the labeled complex was determined to be −2.58. In addition, the in vitro stability of ⁶⁸Ga-NODAGA-LacN-E[c(RGDfK)]₂ was investigated and it was found that it was stable under the examined conditions.

We have established a method for nucleophilic one-pot, two-step radiosynthesis of the popular opioid receptor radioligand 6-O-(2-[¹⁸F]fluoroethyl)-6-O-desmethyl-diprenorphine ([¹⁸F]FE-DPN) from the novel precursor 6-O-(2-tosyloxyethyl)-6-O-desmethyl- 3-O-trityl-diprenorphine (TE-TDDPN), which we designate as the Henriksen precursor. We undertook an optimization of the synthesis conditions, aiming to enhance the accessibility of [¹⁸F]FE-DPN for positron emission tomography (PET) studies of μ-opioid receptors. Herein, we report an optimized direct nucleophilic ¹⁸F-fluorination and the deprotection conditions for a fully automated radiosynthesis of [¹⁸F]FE-DPN on a modified GE Tracerlab FX FE synthesis panel. Starting from 1–1.5 GBq of [¹⁸F]fluoride and applying an Oasis Max 1cc cartridge for fluorine-18 trapping with a reduced amount of K₂CO₃ (5.06 μmol K⁺ ion), [¹⁸F]FE-DPN ([¹⁸F]11) was produced with 44.5 ± 10.6 RCY (decay-corrected), high radiochemical purity (>99%), and a molar activity of 32.2 ± 11.8 GBq/μmol in 60–65 min.

Although radiolabeled alpha-melanocyte stimulating hormone-analogue NAPamide derivatives are valuable melanoma-specific diagnostic probes, their rapid elimination kinetics and high renal uptake may preclude them from being used in clinical settings. We aimed at improving the pharmacokinetics of radiolabeled DOTA-NAPamide compounds by incorporating a 4-(p-iodo-phenyl)-butanoic acid (IPB) into the molecules. Followed by ⁶⁸Ga-, ^205/206Bi-, and ¹⁷⁷Lu-labelling, the radiopharmaceuticals ([⁶⁸Ga]Ga-DOTA-IPB-NAPamide, [^205/206Bi]Bi-DOTA-IPB-NAPamide, [¹⁷⁷Lu]Lu-DOTA-IPB-NAPamide) were characterized in vitro. To test the imaging behavior of the IPB-containing probes, B16F10 tumor-bearing C57BL/6 mice were subjected to in vivo microPET/microSPECT/CT imaging and ex vivo biodistribution studies. All tracers were stable in vitro, with radiochemical purity exceeding 98%. The use of albumin-binding moiety lengthened the in vivo biological half-life of the IPB-carrying radiopharmaceuticals, resulting in elevated tumor accumulation. Both [⁶⁸Ga]Ga-DOTA-IPB-NAPamide (5.06 ± 1.08 %ID/g) and [^205/206Bi]Bi-DOTA-IPB-NAPamide (4.50 ± 0.98 %ID/g) exhibited higher B16F10 tumor concentrations than their matches without the albumin-binding residue ([⁶⁸Ga]Ga-DOTA-NAPamide and [^205/206Bi]Bi-DOTA-NAPamide: 1.18 ± 0.27 %ID/g and 3.14 ± 0.32; respectively), however; the large amounts of off-target radioactivity do not confirm the benefits of half-life extension for short-lived isotopes. Enhanced [¹⁷⁷Lu]Lu-DOTA-IPB-NAPamide tumor uptake even 24 h post-injection proved the advantage of IPB-based prolonged circulation time regarding long-lived radionuclides, although the significant background noise must be addressed in this case as well.

Cyclotron-produced radiometals must be separated from the irradiated target and purified from other metal impurities, which could interfere with the radiolabeling process. We compared different chromatographic and colorimetric methods to determine the amount of transition metals in radioactive samples. Besides commercially available colorimetric tests, 4-(2-pyridylazo)resorcinol and xylenol orange were used as a non-selective metal reagents, forming water-soluble chelates with most of the transition metals immediately. We compared the applicability of pre- and post-column derivatization, as well as colorimetric determination without separation. The studied chromatographic and colorimetric analyses are not suitable to completely replace atomic spectroscopic techniques for the determination of metal contaminants in radioactive samples, but they may play an important role in the development of methods for the purification of radiometals and in their routine quality control.