Malignant lymphomas represent the most common type of hematologic malignancies. The first clinically approved TDD modalities in lymphoma patients were anti-CD20 radioimmunoconjugates (RIT) ¹³¹I-tositumomab and ⁹⁰Y-ibritumomab-tiuxetan. The later clinical success of the first approved antibody–drug conjugate (ADC) for the treatment of lymphomas, anti-CD30 brentuximab vedotin, paved the path for the preclinical development and clinical testing of several other ADCs, including polatuzumab vedotin and loncastuximab tesirine. Other modalities of TDD are based on new formulations of “old” cytostatic agents and their passive trapping in the lymphoma tissue by means of the enhanced permeability and retention (EPR) effect. Currently, the diagnostic and restaging procedures in aggressive lymphomas are based on nuclear imaging, namely PET. A theranostic approach that combines diagnostic or restaging lymphoma imaging with targeted treatment represents an appealing innovative strategy in personalized medicine. The future of theranostics will require not only the capability to provide suitable disease-specific molecular probes but also expertise on big data processing and evaluation. Here, we review the concept of targeted drug delivery in malignant lymphomas from RIT and ADC to a wide array of passively and actively targeted nano-sized investigational agents. We also discuss the future of molecular imaging with special focus on monoclonal antibody-based and monoclonal antibody-derived theranostic strategies.

Multidrug resistance (MDR) is often caused by the overexpression of efflux pumps, such as ABC transporters, in particular, P-glycoprotein (P-gp). Here, we investigate the di- and tri- block amphiphilic polymer systems based on polypropylene glycol (PPO) and copolymers of (N-(2-hydroxypropyl)methacrylamide) (PHPMA) as potential macromolecular inhibitors of P-gp, and concurrently, carriers of drugs, passively targeting solid tumors by the enhanced permeability and retention (EPR) effect. Interestingly, there were significant differences between the effects of di- and tri- block polymer-based micelles, with the former being significantly more thermodynamically stable and showing much higher P-gp inhibition ability. The presence of Boc-protected hydrazide groups or the Boc-deprotection method did not affect the physico-chemical or biological properties of the block copolymers. Moreover, diblock polymer micelles could be loaded with free PPO containing 5–40 wt % of free PPO, which showed increased P-gp inhibition in comparison to the unloaded micelles. Loaded polymer micelles containing more than 20 wt % free PPO showed a significant increase in toxicity; thus, loaded diblock polymer micelles containing 5–15 wt % free PPO are potential candidates for in vitro and in vivo application as potent MDR inhibitors and drug carriers.

Diblock and multiblock polymers of poly(ethylene glycol) containing degradable ester bonds between the blocks were synthesized and characterized. Monofunctional poly(ethylene glycol) (PEG 2000) was modified by aliphatic dicarboxylic acids (malonic, succinic, glutaric, maleic) to obtain monocarboxylic polymers PEG-COOH containing ester bonds. Diblock polymers (4000) were prepared by polycondensation of a diamine (ethane-1,2-diamine, L-lysine) and the semitelechelic PEG-COOH. The relationship between the structure of the linkage connecting two PEG blocks and the rate of its hydrolytic degradation was studied at pH 5.5, 7.4 and 8.0. The rate of hydrolysis of all polymers was significant already under mild alkaline conditions (pH 7.4 and 8.0) and increased with increasing pH. The ester bonds of polymers with saturated dicarboxylic acid moieties were stable at pH 5.5. However, the presence of double bond in the acid moiety substantially decreased the stability of the polymer not only in alkaline but also in acid medium. The results of this model study can be utilized in the design of biodegradable high-molecular-weight drug carriers and polymers for preparation of "stealth" systems intended for therapeutic application.