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

¹⁸F-Mefway PET Imaging of Serotonin 1A Receptors in Humans: A Comparison with ¹⁸F-FCWAY

<div><p>Introduction</p><p>The purpose of this research is to evaluate the prospects for the use of 4-(<i>trans</i>-¹⁸F-fluoranylmethyl)-<i>N</i>-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-<i>N</i>-pyridin-2-ylcyclohexane-1-carboxamide (¹⁸F-Mefway) in comparison to ¹⁸F-<i>trans</i>-4-fluoro-<i>N</i>-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-<i>N</i>-(2-pyridyl)cyclohexanecarboxamide (¹⁸F-FCWAY) for the quantification of 5-HT_1A receptors in human subjects.</p><p>Method</p><p>Five healthy male controls were included for two positron emission tomography (PET) studies: ¹⁸F-FCWAY PET after the pretreatment with 500 mg of disulfiram and two months later, ¹⁸F-Mefway PET without disulfiram. Regional time-activity curves (TACs) were extracted from nine cortical and subcortical regions in dynamic PET images. Using cerebellar cortex without vermis as reference tissue, in vivo kinetics for both radioligands were compared based on the distribution volume ratio (DVR) calculated by non-invasive Logan graphical analysis and area under the curve ratio of the TACs (AUC ratio).</p><p>Result</p><p>Although the pattern of regional uptakes in the ¹⁸F-Mefway PET was similar to that of the ¹⁸F-FCWAY PET (highest in the hippocampus and lowest in the cerebellar cortex), the amount of regional uptake in ¹⁸F-Mefway PET was almost half of that in ¹⁸F-FCWAY PET. The skull uptake in ¹⁸F-Mefway PET was only 25% of that in ¹⁸F-FCWAY PET with disulfiram pretreatment. The regional DVR values and AUC ratio values for ¹⁸F-Mefway were 17—40% lower than those of ¹⁸F-FCWAY. In contrast to a small overestimation of DVR values by AUC ratio values (< 10%) in ¹⁸F-FCWAY PET, the overestimation bias of AUC ratio values was much higher (up to 21%) in ¹⁸F-Mefway PET.</p><p>Conclusion</p><p>As ¹⁸F-Mefway showed lower DVR values and greater overestimation bias of AUC ratio values, ¹⁸F-Mefway may appear less favorable than ¹⁸F-FCWAY. However, in contrast to ¹⁸F-FCWAY, the resistance to <i>in vivo</i> defluorination of ¹⁸F-Mefway obviates the need for the use of a defluorination inhibitor. Thus, ¹⁸F-Mefway may be a good candidate PET radioligand for 5-HT_1A receptor imaging in human.</p></div

Chemical structures of ¹⁸F-FCWAY and ¹⁸F-Mefway.

<p>Chemical structures of ¹⁸F-FCWAY and ¹⁸F-Mefway.</p

Axial PET images of ¹⁸F-FCWAY (upper) and ¹⁸F-Mefway (lower).

<p>Time-averaged images using dynamic PET images of 20–40, 60–80, and 80–100 minute, respectively.</p

Relationship between the DVR and AUC ratio values for ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B). Dashed lines represent identity lines.

<p>Relationship between the DVR and AUC ratio values for ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B). Dashed lines represent identity lines.</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

Comparison of skull uptake in ¹⁸F-FCWAY and ¹⁸F-Mefway PET.

<p>Here, ¹⁸F-FCWAY PET data were acquired with disulfiram pretreatment. Circles and error bars represent mean ± standard error of the mean (SEM) in five healthy controls (closed circle = ¹⁸F-FCWAY, open circle = ¹⁸F-Mefway).</p

Regional time-activity curves of ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B) PET.

<p>Data represent mean values for five healthy controls.</p

Voxel-wise parametric mapping for ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B).

<p>Voxel-wise parametric mapping for ¹⁸F-FCWAY (A) and ¹⁸F-Mefway (B).</p

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