ImmunoPET Imaging of Multiple Myeloma with [68Ga]Ga-NOTA-Nb1053

Purpose Multiple myeloma (MM) remains incurable and its diagnosis relies heavily on bone marrow aspiration and biopsy. CD38 is a glycoprotein highly specific for MM. Antibody therapeutics (e.g., daratumumab) targeting CD38 have shown encouraging efficacy in treating MM, either as a monotherapy agent or in combination with other regimens. However, efficient stratification of patients who might benefit from daratumumab therapy and timely monitoring of the therapeutic responses are still clinical challenges. This work aims to devise a CD38-targeted imaging strategy and assess its value in diagnosing MMs. Methods By labeling a CD38-specific single domain antibody (Nb1053) with 68Ga (t1/2 = 1.1 h), we developed a CD38-targeted immuno-positron emission tomography (immunoPET) imaging probe [68Ga]Ga-NOTA-Nb1053. The probe was developed with good radiochemical yield (> 50%), excellent radiochemical purity (> 99%), and immunoreactivity (> 95%). The diagnostic accuracy of the probe was thoroughly investigated in preclinical MM models. Results ImmunoPET imaging with the probe specifically depicted all the subcutaneous and orthotopic MM lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. More importantly, daratumumab preloading significantly reduced [68Ga]Ga-NOTA-Nb1053 uptake in the disseminated bone lesions, indicating the overlapping targeting epitopes of [68Ga]Ga-NOTA-Nb1053 with that of daratumumab. Furthermore, premedication with sodium maleate or fructose significantly decreased kidney retention of [68Ga]Ga-NOTA-Nb1053 and improved the diagnostic value of the probe in lymphoma models. Conclusion This work successfully developed a novel CD38-targeted immunoPET imaging approach that enabled precise visualization of CD38 and diagnosis of MMs. Upon clinical translation, [68Ga]Ga-NOTA-Nb1053 immunoPET may serve as a valuable CD38-targeted molecular imaging toolbox, facilitating early diagnosis of MM and precise assessment of the therapeutic responses.

Investigation of a Pharmacological Approach for Reduction of Renal Uptake of Radiolabeled ADAPT Scaffold Protein

Albumin binding domain-Derived Affinity ProTeins (ADAPTs) are small (5 kDa) engineered scaffold proteins that are promising targeting agents for radionuclide-based imaging. A recent clinical study has demonstrated that radiolabeled ADAPTs can efficiently visualize human epidermal growth factor receptor 2 (HER2) expression in breast cancer using SPECT imaging. However, the use of ADAPTs directly labeled with radiometals for targeted radionuclide therapy is limited by their high reabsorption and prolonged retention of activity in kidneys. In this study, we investigated whether a co-injection of lysine or gelofusin, commonly used for reduction of renal uptake of radiolabeled peptides in clinics, would reduce the renal uptake of [99mTc]Tc(CO)3-ADAPT6 in NMRI mice. In order to better understand the mechanism behind the reabsorption of [99mTc]Tc(CO)3-ADAPT6, we included several compounds that act on various parts of the reabsorption system in kidneys. Administration of gelofusine, lysine, probenecid, furosemide, mannitol, or colchicine did not change the uptake of [99mTc]Tc(CO)3-ADAPT6 in kidneys. Sodium maleate reduced the uptake of [99mTc]Tc(CO)3-ADAPT6 to ca. 25% of the uptake in the control, a high dose of fructose (50 mmol/kg) reduced the uptake by ca. two-fold. However, a lower dose (20 mmol/kg) had no effect. These results indicate that common clinical strategies are not effective for reduction of kidney uptake of [99mTc]Tc(CO)3-ADAPT6 and that other strategies for reduction of activity uptake or retention in kidneys should be investigated for ADAPT6.

The Improvement of Polymer Structure Related to Radical Treatment of Alveolar Abcesses

Painful periapical manifestations are inflammatory responses of periapical connective tissue to pulpal irritants, when the exudative forces become hyperactive. From the point of view of tooth preservation, apical resection is a valuable procedure in avoiding early edentation, as it is a factual surgical method that comes to aid the conservative endodontic therapy. Polymers are chemical compounds (in most cases organic) with large molecules (macromolecules) obtained from the union of a molecular chain (catena) of a large number of monomers usually with identical structural units. In our research we evaluated the resistance to traction 9 test specimens for which the structure was aimed at the improvement of the self-polymerizable acrylic structure by adding sodium maleate co-polymers, namely maleic anhydride, whose structure was linked to the anti-microbial substances, of the thymol type with controlled release, versions with greater resistance, they found clinical applicability on 244 cases. An increased resistance to fracture was registered for the test specimens II, which unites polymer powder together with the sodium maleate co-polymer, in a ratio of 3 to 1 (F = 1030 and max = 37.73), test specimen III, which unites polymer powder together with the co- anhydride maleic polymer, in a ratio of 3 to 1 (F = 950 and max = 37.88), followed by the same combinations to which it was added the care antibacterial substance, thymol. An important role in the long term in the success of the apical resection, in addition to the applied surgical technique, accrues to the retrograde obturation material, which insures an optimal healing at the peri-apical level insuring the bony apposition at this level.

Frontal Analysis Continuous Capillary Electrophoresis Study on the Interaction of an Amphiphilic Alternating Copolymer with Triton X-100

The interaction of amphiphilic alternating copolymers of sodium maleate and dodecyl vinyl ether (Mal/C12) with a nonionic surfactant, Triton X-100 (TX), was investigated by frontal analysis continuous capillary electrophoresis (FACCE). The binding isotherms obtained from FACCE data were indicative of weak cooperative interaction for all the polymers examined. The cooperative interaction was also analyzed by the Hill model, and the results were compared with the previous results on the interaction of statistical copolymers of sodium 2-acrylamido-2-methylpropanesulfonate andN-dodecylmethacrylamide with TX.