Abstract
This chapter describes briefly some scientific activities common to Richard P. Baum and Kalevi Kairemo. Both started with radioimmunodetection in late 1980s and ended up with radiomolecular precision oncology in 2020s. The author also had own interests which Richard Baum did not touch. The author worked some time with oligonucleotide radionuclide therapy (radionanotargeting) in the 1990s learning that it will be impossible in clinical practice. On the contrary, in spite of his own scepticism, intelligent multidisciplinary targeted nanoparticles could be constructed although being cumbersome. Here radiotheragnostic compounds will play major role. Additionally, some personal aspects are presented in order to honour Richard Baum’s achievements.
Festschrift in Honor of Prof. Dr. Richard P. Baum.
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Keywords
- Radioimmunodetection
- Immunoscintigraphy
- Immuno-PET
- Radionanotargeting
- Radioimmunotherapy
- Radioimmunosynovectomy
- Drug delivery
- Phage display peptides
- Monoclonal antibodies
- Peptide radionuclide receptor therapy
- Dosimetry
- Early response evaluation
- Theragnostics
- Nanoparticles
- Precision oncology
I have been honoured to know Prof. Dr. Richard P. Baum (later Richard) for more than 30 years. Our first encounters happened at the end of 1980s when we both worked with Tc-99m- and In-111-labelled monoclonal antibodies [1,2,3,4,5,6,7,8,9,10,11]. Prof. Dr. Richard P. Baum was then in Frankfurt a Main. Our first meetings took place in European and American Nuclear Medicine conferences or Special monoclonal antibody meetings either in Princeton or San Diego. Typically, Richard Baum was suggesting radical improvements to my work and convincing that his work is much better; anyway, we both made substantial contributions to this field. We started fully new therapies, found new applications and indications, wrote reviews, etc. I considered Richard’s criticism most often as a compliment, because I had caused a reaction. I really felt honoured when Prof. Dr. Richard P. Baum after one Society of Nuclear Medicine conference asked me to show my slides, because he could not attend my presentation. In spite of his criticism, I really did not consider Richard Baum as a competitor because my scientific environment and resources in Helsinki were modest as compared to those Richard was able to gain in Germany. In some occasions, I remember Richard Baum state early 1990s the Americans being “years behind us”. We were actively interacting with each other in many, many conferences, but never really made collaborative research.
We were both active in this field ever since, but moved to smaller molecules. We both introduced new concepts, especially Richard. I started to talk about immuno-PET in mid-1990s instead of complex radioimmunodetection methods [11]. I also screened a new field of radionanotargeting, gene therapy with radionuclides (Fig. 16.1). A long story [12,13,14] in brief was that this therapy would not be feasible based on my subcellular dosimetry results. But I did not fully get rid of new radioimmunodetection methods, because I introduced new methods, e.g. radioimmunosynovectomy in 1990s as well [15]. At this time Richard was very active with peptides, e.g. with his extensive IRIST (International Research Group in Immunoscintigraphy and Immunotherapy) activities. I worked late 1990s in Norway (Norwegian University of Science and Technology).
In the early 2000s I was active in Sweden (Uppsala University Hospital Akademiska), travelling weekly back home to Finland. While I was creating the Uppsala Nuclear Medicine Clinic, Richard was creating Zentralklinik Bad Berka (ZBB) which was early selected as the ENETS Center of Excellence. Simultaneously, I also started a Biotech company in Finland specializing in targeted drug delivery with tumour targeting phage display peptides. We made progress in this field. Due to “financial toxicity” this new multidisciplinary targeting approach was never applied in clinical trials, even though I had funding for it. My hands were tied because of IPR development, hardly published anything for more than 5 years [16]. In Finland, I developed imaging applications for pharmaceutical industry [17]. Table 16.1 summarizes in nutshell the characteristics of multidisciplinary nanoparticles for theragnostic purposes. It is obvious from Table 16.1 that radionuclide methods will allow most clinical radiotheragnostic applications.
After serving as Clinical Director at Advanced Accelerator Applications (AAA) SA in France, I returned to Helsinki in 2009. Then it was the time for Docrates Cancer Center (DCC), the first full-service private oncology clinic in Nordic countries. Because Uppsala was the Neuroendocrinology Center in Nordic countries, I was able to start this activity again in Finland and participate at AAA in designing the LutaThera trial. I also went to Bad Berka to attend the 10-year anniversary of Zentralklinik Bad Berka (ZBB) and for the second time, to present voxel-based dosimetry in the first World Congress on Gallium-68 and Peptide Receptor Radionuclide Therapy (PRRNT) (June 23–26, 2011). In Bad Berka I demonstrated voxel-based dosimetry data in clinical routine [18], the key characteristics are shown in Fig. 16.2.
At Docrates Cancer Center my focus has been development of molecular radiotherapy (later theragnostics) and nuclear medicine. For developing an international cancer centre where patients travel from other countries, special methods should be developed. The methods may be related to response evaluation, such as early response or response prediction. Early response is required to see the possible effect for expensive or sophisticated therapies as early as possible (example Fig. 16.3). Prediction is more important, but more difficult. The world literature is full of prognostic factors, but no real prediction methods exist.
The atmosphere between me and Richard P. Baum has never been competitive, actually, the other way around, stimulating, supportive and synergistic. Our paths have crossed elsewhere as well and in many circumstances. I became very much involved with World Association of Radiopharmaceutical Therapy (WARMTH) since 2007 in Mongolia, by attending every WARMTH conference ever since like Richard. In the role of WARMTH President, Richard and his wife Julitta Rück-Baum visited Finnish Lapland 1 year before Levi Conference in Autumn 2011 (Fig. 16.4). I was in Richard’s very first Theragnostics World Conference in summer 2011 as mentioned earlier [18].
Besides being active in the Scientific program, Richard is typically very active in the social program. In the seventh ICRT meeting in Levi 2012 Richard received the second prize in Tandem Ski Competition between the seven Continents (Fig. 16.5). And the Oenophilous Dinners, wine from participating countries, is a wonderful invention. Membership fee is three Italian Euros. Wife Julitta kept records of these events (Fig. 16.6).
The Richard’s own landmark, the Bad Berka’s ENETS Center of Excellence, Institute for Molecular Radiotherapy, later Theragnostics and Precision Oncology, is a unique hospital, based on Prof. Dr. Richard P. Baum’s dreams to become a fantastic reality. Richard’s own science has been outstanding, typically first injections of new theragnostics tracers, such as the Uppsala affibody molecules [20], new peptides and peptidomimetic compounds in neuroendocrine neoplasms and prostate cancer [21,22,23]. Richard is known all over the world, he has been a speaker in numerous conferences in every continent. A picture taken in Teheran at Asia Oceania Congress of Nuclear Medicine and Biology where I am together with RPB and JRB and two Iranian organizers (Fig. 16.7). The theragnostics work requires very much from the clinician. Knowledge of numerous subspecialties is almost essential, I learned when developing my small clinic in Helsinki a lot about external beam radiation therapy, response assessment and development of response criteria for many cancers [24,25,26,27].
Thousands of patients from all over the world have got cured in ZBB, only because of Richard’s hard work, perseverance and sustainability. The results are extraordinary and there is more to come [28, 29]. I have really been inspired by this and I once again feel really honoured by knowing this great man.
Finally, we have found each other in publications [30, 31]. I know that Richard knows Latin and that he is a friend of deeper understanding and philosophy. So am I, I am a great friend of genealogy. It was written in the stars, that I would become a nuclear medicine physician. Per aspera ad astra. One of my ancestors was Helena von Qvanten (since eight generations) verifying that my family was related with quanta (quantum) before they were even discovered in physics [32]. Another strange omen is my relation to the ancient Danish Kings (28 generations back) [32]. The last one, Knud IV was canonized and a church was erected in Odense in 1086 at the site of his violent death. Odense is a famous place, because of scientists such as the great Finn (E. von Eyben [30]) and Fairytales by Hans Christian Andersen. Actually, the German Fairytale Route (Deutsche Märchestrasse) starts from Hanau, nahe bei Frankfurt (am Main) and ends in Bremen, also connecting my and Richard’s alma maters. My first school abroad was in Bremen in 1973 (Gymnasium an der Parsevalstrasse).
I wish Prof. Dr. Richard P. Baum, the former Chairman and Clinical Director of the Center for Radiomolecular Precision Oncology in Zentralklinik Bad Berka, great success for his new academic initiative in International Centers for Precision Oncology (ICPO).
Sincerely yours
Kalevi Kairemo
Helsinki, January 2020
References
Baum RP, Hertel A, Lorenz M, Schwarz A, Encke A, Hör G. 99Tcm-labelled anti-CEA monoclonal antibody for tumour immunoscintigraphy: first clinical results. Nucl Med Commun. 1989;10(5):345–52. Erratum in: Nucl Med Commun 1989 Oct;10(10):772–3.
Baum RP. Immunoscintigraphy as a diagnostic tool in pancreatic cancer. Hepatogastroenterology. 1989;36(6):459–61. Erratum in: Hepatogastroenterology 1990 Feb;37(1):154.
Baum RP, Adams S, Kiefer J, Niesen A, Knecht R, Howaldt HP, Hertel A, Adamietz IA, Sykes T, Boniface GR, et al. A novel technetium-99m labeled monoclonal antibody (174H.64) for staging head and neck cancer by immuno-SPECT. Acta Oncol. 1993;32(7–8):747–51.
Baum RP, Niesen A, Hertel A, Adams S, Kojouharoff G, Goldenberg DM, Hör G. Initial clinical results with technetium-99m-labeled LL2 monoclonal antibody fragment in the radioimmunodetection of B-cell lymphomas. Cancer. 1994;73(3 Suppl):896–9.
Baum RP, Brümmendorf TH. Radioimmunolocalization of primary and metastatic breast cancer. Q J Nucl Med. 1998;42(1):33–42. Review.
Kairemo KJA, Hopsu EV. Diagnosis of tumors of the parotid gland with anti-CEA immunoscintigraphy. AJR Am J Roentgenol. 1990;154(6):1259–62.
Kairemo KJA, Hopsu EV. Imaging of pharyngeal and laryngeal carcinomas with indium-111-labeled monoclonal anti-CEA antibodies. Laryngoscope. 1990;100(10 Pt 1):1077–82.
Kairemo KJA, Wiklund TA, Liewendahl K, Miettinen M, Heikkonen JJ, Virkkunen PJ, Aronen HJ, Blomqvist CP. Imaging of soft-tissue sarcomas with indium-111-labeled monoclonal antimyosin Fab fragments. J Nucl Med. 1990;31(1):23–31.
99mTc-labeled monoclonal antibody (BW 431/26) reacting with carcinoembryonic antigen in breast cancer. Cancer Res. 1990;50:949s–54s.
Kairemo KJA, Aronen HJ, Liewendahl K, Paavonen T, Heikkonen JJ, Virkkunen P, Mäki-Hokkonen H, Karonen SL, Brownell AL, Mäntylä MJ. Radioimmunoimaging of non-small cell lung cancer with 111In- and 99mTc-labeled monoclonal anti-CEA-antibodies. Acta Oncol. 1993;32(7–8):771–8.
Kairemo KJA. Positron emission tomography of monoclonal antibodies. Acta Oncol. 1993;32(7–8):825–30. Review.
Kairemo KJA, Tenhunen M, Jekunen AP. Oligoradionuclidetherapy using radiolabelled antisense oligodeoxynucleotide phosphorothioates. Anticancer Drug Des. 1996;11(6):439–49.
Kairemo KJA, Tenhunen M, Jekunen AP. Gene therapy using antisense oligodeoxynucleotides labeled with auger-emitting radionuclides. Cancer Gene Ther. 1998;5(6):408–12.
Kairemo KJA, Jekunen AP, Tenhunen M. Dosimetry and optimization of in vivo targeting with radiolabeled antisense oligodeoxynucleotides: oligonucleotide radiotherapy. Methods Enzymol. 2000;314:506–24.
Kairemo KJA, Strömberg S, Nikula TK, Karonen SL. Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory foci using rhenium-188 labelled monoclonal antibody in mice. Cell Adhes Commun. 1998;5(4):325–33.
Penate Medina O, Haikola M, Tahtinen M, Simpura I, Kaukinen S, Valtanen H, Zhu Y, Kuosmanen S, Cao W, Reunanen J, Nurminen T, Saris PE, Smith-Jones P, Bradbury M, Larson SM, Kairemo K. Liposomal tumor targeting in drug delivery utilizing MMP-2- and MMP-9-binding ligands. J Drug Deliv. 2011;2011:160515. Epub 2010 Dec 29. https://doi.org/10.1155/2011/160515.
Kairemo KJA, Tähtinen M. Radiolabeled compounds in the development of cytotoxic agents. Curr Pharm Des. 2004;10(24):2923–34. Review.
Kairemo K, Kangasmäki A. 4D SPECT/CT acquisition for 3D dose calculation and dose planning in (177)Lu-peptide receptor radionuclide therapy: applications for clinical routine. Recent Results Cancer Res. 2013;194:537–50. https://doi.org/10.1007/978-3-642-27994-2_31.
Kairemo K, Santos EB, Macapinlac HA, Subbiah V. Early response assessment to targeted therapy using 3′-deoxy-3′[(18)F]-Fluorothymidine (18F-FLT) PET/CT in lung cancer. Diagnostics. 2020;10(1):26.
Baum RP, Prasad V, Müller D, Schuchardt C, Orlova A, Wennborg A, Tolmachev V, Feldwisch J. Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. J Nucl Med. 2010;51(6):892–7. Epub 2010 May 19. https://doi.org/10.2967/jnumed.109.073239.
Baum RP, Kulkarni HR, Carreras C. Peptides and receptors in image-guided therapy: theranostics for neuroendocrine neoplasms. Semin Nucl Med. 2012;42(3):190–207. https://doi.org/10.1053/j.semnuclmed.2012.01.002.
Baum RP, Kulkarni HR, Müller D, Satz S, Danthi N, Kim YS, Brechbiel MW. First-in-human study demonstrating tumor-angiogenesis by PET/CT imaging with (68)Ga-NODAGA-THERANOST, a high-affinity Peptidomimetic for αvβ3 integrin receptor targeting. Cancer Biother Radiopharm. 2015;30(4):152–9. https://doi.org/10.1089/cbr.2014.1747.
Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, Schottelius M, Mueller D, Klette I, Wester HJ. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57(7):1006–13. Epub 2016 Jan 21. https://doi.org/10.2967/jnumed.115.168443.
Kairemo KJ. PET/computed tomography for radiation therapy planning of prostate cancer. PET Clin. 2017;12(2):257–67. Epub 2017 Jan 31. Review. https://doi.org/10.1016/j.cpet.2016.12.003.
Kairemo K, Joensuu T. Radium-223-dichloride in castration resistant metastatic prostate cancer-preliminary results of the response evaluation using F-18-fluoride PET/CT. Diagnostics (Basel). 2015;5(4):413–27. https://doi.org/10.3390/diagnostics5040413.
Kairemo K, Ravizzini GC, Macapinlac HA, Subbiah V. An assessment of early response to targeted therapy via molecular imaging: a pilot study of 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography 18F-FLT PET/CT in prostate adenocarcinoma. Diagnostics (Basel). 2017;7(2):E20. https://doi.org/10.3390/diagnostics7020020.
Kairemo K, Rohren EM, Anderson PM, Ravizzini G, Rao A, Macapinlac HA, Subbiah V. Development of sodium fluoride PET response criteria for solid tumours (NAFCIST) in a clinical trial of radium-223 in osteosarcoma: from RECIST to PERCIST to NAFCIST. ESMO Open. 2019;4(1):e000439. https://doi.org/10.1136/esmoopen-2018-000439.eCollection.2019.
Baum RP, Singh A, Schuchardt C, Kulkarni HR, Klette I, Wiessalla S, Osterkamp F, Reineke U, Smerling C. 177Lu-3BP-227 for Neurotensin receptor 1-targeted therapy of metastatic pancreatic adenocarcinoma: first clinical results. J Nucl Med. 2018;59(5):809–14. Epub 2017 Oct 12. https://doi.org/10.2967/jnumed.117.193847.
Baum RP, Kulkarni HR, Singh A, Kaemmerer D, Mueller D, Prasad V, Hommann M, Robiller FC, Niepsch K, Franz H, Jochems A, Lambin P, Hörsch D. Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms. Oncotarget. 2018;9(24):16932–50.
von Eyben FE, Singh A, Zhang J, Nipsch K, Meyrick D, Lenzo N, Kairemo K, Joensuu T, Virgolini I, Soydal C, Kulkarni HR, Baum RP. 177Lu-PSMA radioligand therapy of predominant lymph node metastatic prostate cancer. Oncotarget. 2019;10(25):2451–61.
Tulchinsky M, Baum RP, Bennet KG, Freeman LM, Jong I, Kairemo K, Marcus CS, Moadel RM, Suman P. Well-founded recommendations for radioactive iodine treatment of differentiated thyroid cancer require balanced study of benefits and harms. J Clin Oncol. 2018;36(18):1887–8. Epub 2018 May 3. https://doi.org/10.1200/JCO.2018.78.5972.
Rantala O-P. Henrik Trapp, esi-isät ja jälkeläiset (Henrik Trapp, ancestors and descendants). Helsinki; 2019. p. 163.
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Kairemo, K. (2024). From Radioimmunodetection to Radiomolecular Precision Oncology Via Radionanotargeting by Intelligent Multidisciplinary Radiotheragnostic Nanoparticles. In: Prasad, V. (eds) Beyond Becquerel and Biology to Precision Radiomolecular Oncology: Festschrift in Honor of Richard P. Baum. Springer, Cham. https://doi.org/10.1007/978-3-031-33533-4_16
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