Efficient Radiolabeling of Proteins and Antibodies via Maleamate–Cysteine Bioconjugation

The study introduces a novel maleamate-based prosthetic group specifically designed for efficient, site-specific radioiodination of biomolecules that contain or are modified with cysteine residues. This strategy is a compelling alternative to the conventional maleimide-based approach, demonstrating outstanding attributes such as high radiochemical yield, rapid reaction kinetics, applicability in aqueous media at neutral pH, and exceptional stability under a competitive environment

Heteronuclear Gd-^99mTc Complex of DTPA-Bis(histidylamide) Conjugate as a Bimodal MR/SPECT Imaging Probe

The work describes the synthesis and in vivo application of heterotrimetallic complexes of the type {Gd­(H₂O)­[(M­(H₂O)­(CO)₃)₂(<b>1</b>)]} {<b>1</b> = DTPA-bis­(histidyl-amide); <i>M</i> = Re (<b>3a</b>); ^99mTc (<b>3b</b>)} for dual modality MR/SPECT imaging. Here, the DTPA-bis­(histidylamide) conjugate functions as a trinucleating chelate incorporating Gd in the DTPA core with Re or ^99mTc in the pair of histidylamide side arms. The two complexes are chemically equivalent as revealed by HPLC, and their “cocktail mixture” (<b>3a</b> + <b>3b</b>) has demonstrated itself to be essentially a single bimodal imaging probe. The present system has thus overcome the sensitivity difference problem between MRI and SPECT and paved the way for practical applications

New Macrobicyclic Chelator for the Development of Ultrastable ⁶⁴Cu-Radiolabeled Bioconjugate

Ethylene cross-bridged cyclam with two acetate pendant arms, ECB-TE2A, is known to form the most kinetically stable ⁶⁴Cu complexes. However, its usefulness as a bifunctional chelator is limited because of its harsh radiolabeling conditions. Herein, we report new cross-bridged cyclam chelator for the development of ultrastable ⁶⁴Cu-radiolabeled bioconjugates. Propylene cross-bridged TE2A (PCB-TE2A) was successfully synthesized in an efficient way. The Cu­(II) complex of PCB-TE2A exhibited much higher kinetic stability than ECB-TE2A in acid decomplexation studies, and also showed high resistance to reduction-mediated demetalation. Furthermore, the quantitative radiolabeling of PCB-TE2A with ⁶⁴Cu was achieved under milder conditions compared to ECB-TE2A. Biodistribution studies strongly indicate that the ⁶⁴Cu complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation

Operative view.

<p>A. Normal vascular anatomoy of rat. B. Partial devascularization was done by ligating the left gastric artery and short gastric arteries. C. The esophageal-gastric junction was then incised around 50% of the circumference, leaving the small bridge of tissue at posterior part of esophagogastric junction. D. The esophagogastric anastomosis was sutured with interrupted 5–0 polypropylene sutures. E. Operative pictures after all procedures in operation group. F. After microPET imaging, the stomach was incised along the lesser curvature to obtain autoradiographic images.</p

The correlations between expression of immunohistochemistry and PET parameters.

<p>A. HIF-1a expression and %ID/g (Pearson correlation 0.534, <i>p</i><0.001). B. HIF-1a expression and Fundus/Liver ratio (Pearson correlation 0.593, <i>p</i><0.001). C. Pimonidazole expression and %ID/g (Pearson correlation 0.386, <i>p</i> = 0.007). D. Pimonidazole expression and Fundus/Liver ratio (Pearson correlation 0.483, <i>p</i> = 0.001).</p

MicroPET imaging.

<p>A. Operation group. 64Cu-ATSM uptake was observed in the fundus (dotted line). B. Control group. 64Cu-ATSM uptake was not observed in the fundus. C. Comparison of %ID/g values between the operation and control groups. D. Comparison of the fundus/liver ratio (%ID/g of fundus area by %ID/g of liver) between the operation and control groups.</p

Immunohistochemistry.

<p>A. HIF-1a expression in the fundus of the operation group. B. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were expressed in the fundus. C. HIF-1a expression in the fundus of the control group. D. Pimonidazole expression in the fundus of the control group. Pimonidazole and HIF-1a were not expressed in the fundus. E. Comparison of HIF-1a expression levels between the fundus and greater curvature in each group. F. Comparison of pimonidazole expression levels between the fundus and greater curvature in each group. HIF-1a and pimonidazole expression was significantly higher in the fundus than the greater curvature in the operation group.</p

Gadolinium Complex of ¹²⁵I/¹²⁷I‑RGD-DOTA Conjugate as a Tumor-Targeting SPECT/MR Bimodal Imaging Probe

The work describes the synthesis and in vivo application of [Gd­(L)­(H₂O)]·<i>x</i>H₂O, where L is a (¹²⁵I/¹²⁷I-RGD)- DOTA conjugate, as a tumor-targeting SPECT/MR bimodal imaging probe. Here, (¹²⁵I/¹²⁷I-RGD)-DOTA signifies a “cocktail mixture” of radioisotopic (<b>1a</b>, L = ¹²⁵I-RGD-DOTA) and natural (<b>1b</b>, L = ¹²⁷I-RGD-DOTA) Gd complexes. The two complexes are chemically equivalent as revealed by HPLC, and their cocktail mixture exhibits the integrin-specific tumor enhancement, demonstrating that they constitute essentially a single bimodal imaging probe. Employment of a cocktail mixture thus proves to be a sole and practical approach to overcome the sensitivity difference problem between MRI and SPECT

Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (⁶⁸Ga/⁶⁴Cu) and therapy (¹⁷⁷Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which ¹⁷⁷Lu-L1 exhibited markedly higher uptake in HeLa cells than the ¹⁷⁷Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of ⁶⁸Ga-L1 and ⁶⁴Cu-L1 was clearly visualized in the tumor site, while ¹⁷⁷Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when ⁶⁸Ga-L1 or ⁶⁴Cu-L1 is used for diagnosis, ¹⁷⁷Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other

Phosphonate Pendant Armed Propylene Cross-Bridged Cyclam: Synthesis and Evaluation as a Chelator for Cu-64

A propylene cross-bridged macrocyclic chelator with two phosphonate pendant arms (PCB-TE2P) was synthesized from cyclam. Various properties of the synthesized chelator, including Cu-complexation, Cu-complex stability, ⁶⁴Cu-radiolabeling, and in vivo behavior, were studied and compared with those of a previously reported propylene cross-bridged chelator (PCB-TE2A)