Abstract
The use of radiolabeled chemotherapeutics is an exciting prospect in the management of cancer, as lethal cytotoxic radiation dose can be delivered to the cancerous lesions by using minimum amount of chemotherapy drugs, thereby without exerting significant chemotoxic dose burden to the patients, and thus overcoming one of the serious impediments of chemotherapeutic interventions. There is a huge array of natural and synthetic chemotherapeutic drugs, which find regular use in cancer therapy. Radiolabeling some of these drugs with suitable therapeutic radionuclides have been achieved successfully and these radiolabeled agents have shown considerable promise in the pre-clinical studies. This article archives the efforts directed towards developing radiolabeled chemotherapeutics for therapeutic intervention of cancers and results obtained till date with such agents.
Similar content being viewed by others
References
Greenhalgh TA, Symonds RP (2014) Principles of chemotherapy and radiotherapy. Obstet Gynaecol Reprod Med 24:259–265
Lind MJ (2008) Principles of cytotoxic chemotherapy. Medicine 36:19–23
Abotaleb M, Kubatka P, Caprnda M, Varghese E, Zolakova B, Zubor P, Opatrilova R, Kruzliak P, Stefanicka P, Busselberg D (2018) Chemotherapeutic agents for the treatment of metastatic breast cancer: an update. Biomed Pharmacother 101:458–477
Chabner BA, Roberts TG (2005) Chemotherapy and the war on cancer. Nat Rev Cancer 5:65–72
Espinosa E, Zamora P, Feliu J, Barón MG (2003) Classification of anticancer drugs: a new system based on therapeutic targets. Cancer Treat Rev 29:515–523
Schirrmacher V (2019) From chemotherapy to biological therapy: a review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol 54:407–419
Shewach DS, Kuchta RD (2009) Introduction to cancer chemotherapeutics. Chem Rev 109:2859–2861
Tannock IF (1998) Conventional cancer therapy: Promise broken or promise delayed? The Lancet 351:SII–SII16
Abdulkareem I, Zurmi I (2012) Review of hormonal treatment of breast cancer. Niger J Clin Pract 15:9–14
Abraham J, Ocen J, Staffurth J (2023) Hormonal therapy for cancer. Medicine 51:28–31
Chen W, Yuan Y, Jiang X (2020) Antibody and antibody fragments for cancer immunotherapy. J Control Release 328:395–406
Melief CJ (2021) The future of immunotherapy. Immunother Adv 1:1–2
Scott AM, Wolchok JD, Old LJ (2012) Antibody therapy of cancer. Nat Rev Cancer 12:278–287
Weiner LM, Murray JC, Shuptrine CW (2012) Antibody-based immunotherapy of cancer. Cell 148:1081–1084
Weiner LM, Surana R, Wang S (2010) Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 10:317–327
Ersahin D, Doddamane I, Cheng D (2011) Targeted radionuclide therapy. Cancers 3:3838–3855
Sgouros G, Bodei L, McDevitt MR, Nedrow JR (2020) Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat Rev Drug Discov 19:589–608
Boussios S, Pentheroudakis G, Katsanos K, Pavlidis N (2012) Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management. Ann Gastroenterol 5:106–118
Eckford PD, Sharom FJ (2009) ABC efflux pump-based resistance to chemotherapy drugs. Chem Rev 109:2989–3011
Mellor HR, Callaghan R (2008) Resistance to chemotherapy in cancer: a complex and integrated cellular response. Pharmacology 81:275–300
Pan ST, Li ZL, He ZX, Qiu JX, Zhou SF (2016) Molecular mechanisms for tumour resistance to chemotherapy. Clin Exp Pharmacol Physiol 43:723–737
Pritchard JR, Lauffenburger DA, Hemann MT (2012) Understanding resistance to combination chemotherapy. Drug Resist Updates 15:249–257
Arumov A, Trabolsi A, Schatz JH (2021) Potency meets precision in nano-optimized chemotherapeutics. Trends Biotechnol 39:974–977
Fymat AL (2017) Nano chemotherapy: an emergent anti-cancer modality. Glob J Nanomed 1:1–6
Jeon J (2019) Review of therapeutic applications of radiolabeled functional nanomaterials. Int J Mol Sci 20:2323
Wu W, Pu Y, Shi J (2022) Nanomedicine-enabled chemotherapy-based synergetic cancer treatments. J Nanobiotechnol 20:1–21
Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, Wu S, Deng Y, Zhang J, Shao A (2020) Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance. Front Mol Biosci 7:193
Hu MJ, Zhang L (2012) Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem Pharmacol 83:1104–1111
Lei F, Xi X, Batra SK, Bronich TK (2019) Combination therapies and drug delivery platforms in combating pancreatic cancer. J Pharmacol Exp Ther 370:682–694
Reza BM, Tina SH, Narges B, Evgeniya M, Sushil K, Bikul D, Herman Y (2017) Combination therapy in combating cancer. Oncotarget 8:3822–3843
Ku A, Facca VJ, Cai Z, Reilly RM (2019) Auger electrons for cancer therapy: a review. EJNMMI Radiopharm Chem 4:1–36
Thorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, Altman RB (2011) Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genom 21:440
Pang B, De Jong J, Qiao X, Wessels LF, Neefjes J (2015) Chemical profiling of the genome with anti-cancer drugs defines target specificities. Nat Chem Biol 11:472–480
Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, Van Tellingen O (2013) Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin. Nat Commun 4:1–13
Araujo F, Proença F, Ferreira C, Ventilari S, Rosado de Castro P, Moreira R, Fonseca L, Souza S, Gutfilen B (2015) Use of 99mTc-doxorubicin scintigraphy in females with breast cancer: a pilot study. Br J Radiol 88:20150268
Bao A, Goins B, Klipper R, Negrete G, Phillips WT (2004) Direct 99mTc labeling of pegylated liposomal doxorubicin (Doxil) for pharmacokinetic and non-invasive imaging studies. J Pharmacol Exp Ther 308:419–425
Kumar P, Singh B, Ghai A, Hazari PP, Mittal B, Mishra AK (2015) Development of a single vial kit formulation of [99mTc]-labeled doxorubicin for tumor imaging and treatment response assessment-preclinical evaluation and preliminary human results. J Label Compd Radiopharm 58:242–249
Kumar P, Watts A, Acharya P, Bansal R, Ghai A, Kaur A, Singh B (2016) Radiosynthesis of [18F]-fluorobenzoate-doxorubicin using acylation approach. Curr Radiopharm 9:215–221
Soundararajan A, Bao A, Phillips WT, Perez R, Goins BA (2009) [(186)Re]- Liposomal doxorubicin (Doxil): in vitro stability, pharmacokinetics, imaging and biodistribution in a head and neck squamous cell carcinoma xenograft model. Nucl Med Biol 36:515–524
Soundararajan A, Bao A, Phillips WT, McManus LM, Goins BA (2011) Chemoradionuclide therapy with 186Re-labeled liposomal doxorubicin: toxicity, dosimetry, and therapeutic response. Cancer Biother Radiopharm 26:603–614
Liu Y, Yu XM, Sun RJ, Pan XL (2017) Folate-functionalized lipid nanoemulsion to deliver chemo-radiotherapeutics together for the effective treatment of nasopharyngeal carcinoma. AAPS Pharm Sci Tech 18:1374–1381
Ji A, Zhang Y, Lv G, Lin J, Qi N, Ji F, Du M (2018) 131I radiolabeled immune albumin nanospheres loaded with doxorubicin for in vivo combinatorial therapy. J Label Compd Radiopharm 61:362–369
Zhu J, Yang J, Zhao L, Zhao P, Yang J, Zhao J, Miao W (2021) 131I-labeled multifunctional polyethylenimine/doxorubicin complexes with pH-controlled cellular uptake property for enhanced SPECT imaging and chemo/radiotherapy of tumors. Int J Nanomed 16:5167
Cytryniak A, Nazaruk E, Bilewicz R, Górzyńska E, Żelechowska-Matysiak K, Walczak R, Mames A, Bilewicz A, Majkowska-Pilip A (2020) Lipidic cubic-phase nanoparticles (cubosomes) loaded with doxorubicin and labeled with 177Lu as a potential tool for combined chemo and internal radiotherapy for cancers. Nanomaterials 10:2272
El-Kawy O, Talaat H (2016) Preparation, characterization and evaluation of 186Re-idarubicin: a novel agent for diagnosis and treatment of hepatocellular carcinoma. J Label Compd Radiopharm 59:72–77
El-Kawy O, Abdelaziz G (2022) Preparation, characterization and evaluation of [125I]-pirarubicin: a new therapeutic agent for urinary bladder cancer with potential for use as theranostic agent. Appl Radiat Isot 179:110007
Mizutani H, Hotta S, Nishimoto A, Ikemura K, Miyazawa D, Ikeda Y, Maeda T, Yoshikawa M, Hiraku Y, Kawanishi S (2017) Pirarubicin, an anthracycline anticancer agent, induces apoptosis through generation of hydrogen peroxide. Anticancer Res 37:6063–6069
Alvarellos ML, Lamba J, Sangkuhl K, Thorn CF, Wang L, Klein DJ, Altman RB, Klein TE (2014) Pharm GKB summary: gemcitabine pathway. Pharmacogenet Genom 24:564–574
Cerqueira NM, Fernandes PA, Ramos MJ (2007) Understanding ribonucleotidereductase inactivation by gemcitabine. Chem Eur J 13:8507–8515
Mini E, Nobili S, Caciagli B, Landini I, Mazzei T (2006) Cellular pharmacology of gemcitabine. Ann Oncol 17:v7–v12
Dhande R, Tyagi A, Sharma RK, Thakkar H (2017) Biodistribution study of 99mTc-gemcitabine-loaded spherulites in Sprague-Dawley rats by gamma scintigraphy to investigate its lung targeting potential. J Microencapsul 34:623–634
El-Mabhouh AA, Angelov CA, Cavell R, Mercer JR (2006) A 99mTc-labeled gemcitabine bisphosphonate drug conjugate as a probe to assess the potential for targeted chemotherapy of metastatic bone cancer. Nucl Med Biol 33:715–722
Ghosh S, Das T, Sarma HD, Dash A (2018) The potential of radiolabeled chemotherapeutics in tumor diagnosis: preliminary investigations with 68Ga-gemcitabine. Drug Dev Res 79:111–118
El-Mabhouh AA, Mercer JR (2008) 188Re-labelled gemcitabine/bisphosphonate (Gem/BP): a multi-functional, bone-specific agent as a potential treatment for bone metastases. Eur J Nucl Med 35:1240–1248
Ghosh S, Das T, Sarma HD, Dash A (2017) Preparation and evaluation of 177Lu-Labeled gemcitabine: an effort toward developing radiolabeled chemotherapeutics for targeted therapy applications. Cancer Biother Radiopharm 32:239–246
El-Ghany E, Mahdy M, Attallah K, Ghazy F (2002) Preparation of 125I-cytarabine and its radiochemical evaluation: model of radio-therapeutic agent. J Radioanal Nucl Chem 252:165–169
Bayoumi NA, Amin AM, Ismail NS, Abouzid KA, El-Kolaly MT (2015) Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy. Radiochim Acta 103:777–787
Areberg J, Johnsson A, Wennerberg J (2000) In vitro toxicity of 191Pt-labeled cisplatin to a human cervical carcinoma cell line (ME-180). Int J Radiat Oncol Biol Phys 46:1275–1280
Areberg J, Wennerberg J, Johnsson A, Norrgren K, Mattsson S (2001) Antitumor effect of radioactive cisplatin (191Pt) on nude mice. Int J Radiat Oncol Biol Phys 49:827–832
Bodnar EN, Dikiy MP, Medvedeva EP (2015) Photonuclear production and antitumor effect of radioactive cisplatin (195mPt). J Radioanal Nucl Chem 305:133–138
Obata H, Tsuji AB, Sudo H, Sugyo A, Minegishi K, Nagatsu K, Ogawa M, Zhang MR (2021) In vitro evaluation of no-carrier-added radiolabeled cisplatin ([189,191Pt] cisplatin) emitting auger electrons. Int J Mol Sci 22:4622
Tang QS, Chen DZ, Xue WQ, Xiang JY, Gong YC, Zhang L, Guo CQ (2011) Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo. Int J Nanomed 6:3077–3085
Amin A, Farrag N, AbdEl-Bary A (2014) Iodine-125-chlorambucil as possible radio anticancer for diagnosis and therapy of cancer: preparation and tissue distribution. J Pharm Res Int 4:1873–1885
Aslan O, Muftuler FZB, Kilcar AY, Ichedef C, Unak P (2012) In vivo biological evaluation of 131I radiolabeled-paclitaxel glucuronide (131I-PAC-G). Radiochim Acta 100:339–345
Tian L, Chen Q, Yi X, Wang G, Chen J, Ning P, Yang K, Liu Z (2017) Radionuclide I-131 labeled albumin-paclitaxel nanoparticles for synergistic combined chemo-radioisotope therapy of cancer. Theranostics 7:614–623
Gibbens-Bandala B, Morales-Avila E, Ferro-Flores G, Santos-Cuevas C, Meléndez-Alafort L, Trujillo-Nolasco M, Ocampo-García B (2019) 177Lu-Bombesin-PLGA (paclitaxel): a targeted controlled-release nanomedicine for bimodal therapy of breast cancer. Mater Sci Eng C 105:110043
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Jain, A., Das, T. Radiolabeled chemotherapeutics as a novel strategy for targeted cancer therapy: current insights and future perspectives. J Radioanal Nucl Chem 333, 1–15 (2024). https://doi.org/10.1007/s10967-023-09250-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10967-023-09250-3