Keywords

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).

Fig. 16.1
4 illustrations of nano-targeting oligonucleotide radiotherapy. The nucleus has D N A, a double-stranded D N A, a chain of antisense oligomers, and a labeled oligonucleotide phosphorothioate.

Principle of radionanotargeting with antisense oligonucleotides. Nucleus in a cell schematically (a). 3-D presentation of a DNA double strand (b). Possible triplex formation of an antisense oligonucleotide in a close vicinity of DNA double strand (c). Sulphur (S) or phosphorus (P) atoms are substituted with radioactive 35S-, 32P- or 33P-atoms in oligonucleotide phosphorothioates (d). Oligonucleotide radiotherapy in mid 1990s from [14]. Nanotargeting describes nanometer scale events by antibodies or antisense oligonucleotides. Radioactive sulphur or phosphorus atoms substitute the same atoms in oligonucleotide phosphorothioates, and emitted radiation affects structures close to the binding site of the targeting molecule. Antisense oligonucleotides serve as vehicles for radionuclides, enhancing targeting efficacy

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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.

Table 16.1 Summary of the differences between imaging modalities and their possibilities for nanoparticle applications
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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.

Fig. 16.2
8 illustrations of the dose received by the thoracic region. Fluorescence is present in cum act and dose with a tumor in the chest cavity. There is a decreasing trend in the dose kernel graph. A coronal reconstruction of the thoracic cavity with relative dose and anatomy. A linear graph is for the tumors.

Principle of voxel-based dosimetry for clinical routine. Serial 3D SPECT data allow voxel half-life calculations, which are multiplied by radionuclide characteristics (dose point kernels) in order to obtain absorbed radiation doses in Gy’s. With hybrid imaging (SPECT/CT) Gy’s can be located anatomically. This method suits also for dose prediction. On the right it is shown in seven patients that tumor and liver doses can be predicted from pre-therapeutic voxel-based dosimetric data using diagnostic doses. The prediction overestimated kidney and spleen doses. (Presented in 2011. Partly published in [18])

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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.

Fig. 16.3
10 illustrations of the axial and coronal sections of the patient with a tumor in the chest cavity that has greater intensity with the surrounding tissues as indicated by an arrow. The arrangement of purine and pyrimidines is present in the D N A. The chemical structure of thymidine and F L T is observed.

Example of early response assessment in a new targeted therapy for lung cancer. Radiolabelled nucleotide analogue for DNA acts as surrogate marker for cellular proliferation rapidly. Here, a clear response is seen in 9 days. (Presented in the Graphical Abstract of [19])

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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].

Fig. 16.4
A photo of the front side of Kittila.

Richard Baum, Julitta Rück-Baum and Kalevi Kairemo in Lapland in 2011

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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).

Fig. 16.5
A photo of a group of people and Doctor Richard on the snowy mountains.

Richard Baum (in blue) receiving the second Prize in the WC of Tandem Skiing. (From Kalevi Kairemo, in grey/ red) in Lapland in 2012

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Fig. 16.6
A photo of a table with many bottles of alcohol.

Oenophilous Dinner in Lapland 2012

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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].

Fig. 16.7
A group photograph of Richard with R P B, J R B, and 2 female organizers.

The author and RPB and Julitta with Iranian hosts at AONMB Congress in Teheran

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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