Dosimetry of 177Lu-DOTATOC First Circle Treatment in Patients With Advanced Metastatic Neuroendocrine Tumors: a Pilot Study in China

Abstract Objective: The aim of this study was to calculate the dosimetry of 177Lu-DOTATOC in the first circle of peptide receptor radionuclide treatment (PRRT) in patients with advanced neuroendocrine tumors (NETs). Patients and Methods: Eight patients (4 female, 4 male) with NETs were enrolled in this study. All these patients with unresectable primary lesion and multiple metastasis received 177Lu-DOTATOC treatment with a single activity of 1.59-3.49 GBq (43.1-94.2 mCi) and underwent a series of whole-body planar scan at 0.5 h, 24 h, 48 h and 72 h and SPECT/CT scan at 24 h after injection. The region of interest (ROI) was drawn on the primary and metastatic lesion, the mediastinum served as control area. Therefore, the ratio of tumor-to-mediastinum (T/NT) was also calculated. The Hermes hybrid viewer dosimetry module together with OLINDA/EXM 2.0 was used to determine absorbed doses of organs and tumors. Results: No significant changes in both laboratory test was found after 177Lu-DOTATOC treatment, including renal function and blood cell analysis ( F= 0.047-1.062, P =0.364-0.959). Physiological uptake of 177Lu-DOTATOC was seen in the liver, the spleen and the kidneys. Focal uptake of 177Lu-DOTATOC was found in the tumors including primary tumors and metastatic lesions, the ratio of T/NT was 39.45 ± 28.83. The residence time of 177Lu-DOTATOC was 0.82 ± 0.12 h for left kidney, 0.80 ± 0.15 h for right kidney, 1.35 ± 0.89 h for spleen, 1.80± 2.70 h for tumors, and 30.21 ± 11.29 h for total body. Organs with the highest absorbed doses per injected activity were tumors (1.2936 ± 0.8625 mGy/MBq), spleen (0.4608 ± 0.4084 mGy/MBq), and kidneys (0.3843 ± 0.1120 mGy/MBq). The mean effective dose was 0.0392 ± 0.0158 mSv/MBq with the range of 0.0158-0.0674 mSv/MBq. In addition, Photon cross-irradiation was found to reach 19.46 % in adrenals, whereas photon can contribute less than 3% of the kidneys’ total dose. Conclusion: This study demonstrates that absorbed dose in the kidneys and spleen are relatively lower, whereas the tumor shows longer retention time and higher internal radiation absorbed dose in PRRT. PRRT is a well-tolerated treatment strategy. 177Lu-DOTATOC SPECT /CT serves as independent predictor for the evaluation of response to PRRT, which contributes to predict the response to PRRT and the related adversity.

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First-In-Human Results on the Biodistribution, Pharmacokinetics, and Dosimetry of [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2

Pharmaceuticals ◽

10.3390/ph14121212 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1212

Author(s):

Sanjana Ballal ◽

Madhav Prasad Yadav ◽

Euy Sung Moon ◽

Vasko S Kramer ◽

Frank Roesch ◽

...

Keyword(s):

Urinary Bladder ◽

Gall Bladder ◽

Oral Mucosa ◽

Absorbed Dose ◽

Left Colon ◽

Whole Body ◽

Lacrimal Glands ◽

Right Colon ◽

Physiological Uptake ◽

Absorbed Doses

Recently, great interest has been gained regarding fibroblast activation protein (FAP) as an excellent target for theranostics. Several FAP inhibitor molecules such as [68Ga]Ga-labelled FAPI-02, 04, 46, and DOTA.SA.FAPi have been introduced and are highly promising molecular targets from the imaging point of view. FAP inhibitors introduced via bifunctional DOTA and DOTAGA chelators offer the possibility to complex Lutetium-177 due to an additional coordination site, and are suitable for theranostic applications owing to the increased tumor accumulation and prolonged tumor retention time. However, for therapeutic applications, very little has been accomplished, mainly due to residence times of the compounds. In an attempt to develop a promising therapeutic radiopharmaceutical, the present study aimed to evaluate and compare the biodistribution, pharmacokinetics, and dosimetry of [177Lu]Lu-DOTA.SA.FAPi, and [177Lu]Lu-DOTAGA.(SA.FAPi)2 in patients with various cancers. The FAPi agents, [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2, were administered in two different groups of patients. Three patients (mean age—50 years) were treated with a median cumulative activity of 2.96 GBq (IQR: 2.2–3 GBq) [177Lu]Lu-DOTA.SA.FAPi and seven (mean age—51 years) were treated with 1.48 GBq (IQR: 0.6–1.5) of [177Lu]Lu-DOTAGA.(SA.FAPi)2. Patients in both the groups underwent serial imaging whole-body planar and SPECT/CT scans that were acquired between 1 h and 168 h post-injection (p.i.). The residence time and absorbed dose estimate in the source organs and tumor were calculated using OLINDA/EXM 2.2 software. Time versus activity graphs were plotted to determine the effective half-life (Te) in the whole body and lesions for both the radiotracers. Physiological uptake of [177Lu]Lu-DOTA.SA.FAPi was observed in the kidneys, colon, pancreas, liver, gall bladder, oral mucosa, lacrimal glands, and urinary bladder contents. Physiological biodistribution of [177Lu]Lu-DOTAGA.(SA.FAPi)2 involved liver, gall bladder, colon, pancreas, kidneys, and urinary bladder contents, lacrimal glands, oral mucosa, and salivary glands. In the [177Lu]Lu-DOTA.SA.FAPi group, the highest absorbed doses were noted in the kidneys (0.618 ± 0.015 Gy/GBq), followed by the colon (right colon: 0.472 Gy/GBq and left colon: 0.430 Gy/GBq). In the [177Lu]Lu-DOTAGA.(SA.FAPi)2 group, the colon received the highest absorbed dose (right colon: 1.160 Gy/GBq and left colon: 2.870 Gy/GBq), and demonstrated a significantly higher mean absorbed dose than [177Lu]Lu-DOTA.SA.FAPi (p < 0.011). [177Lu]Lu-DOTAGA.(SA.FAPi)2 had significantly longer median whole-body Te compared to that of [177Lu]Lu-DOTA.SA.FAPi [46.2 h (IQR: 38.5–70.1) vs. 23.1 h (IQR: 17.8–31.5); p-0.0167]. The Te of tumor lesions was significantly higher for [177Lu]Lu-DOTAGA.(SA.FAPi)2 compared to [177Lu]Lu-DOTA.SA.FAPi [86.6 h (IQR: 34.3–94.6) vs. 14 h (IQR: 12.8–15.5); p-0.0004]. The median absorbed doses to the lesions were 0.603 (IQR: 0.230–1.810) Gy/GBq and 6.70 (IQR: 3.40–49) Gy/GBq dose per cycle in the [177Lu]Lu-DOTA.SA.FAPi, and [177Lu]Lu-DOTAGA.(SA.FAPi)2 groups, respectively. The first clinical dosimetry study demonstrated significantly higher tumor absorbed doses with [177Lu]Lu-DOTAGA.(SA.FAPi)2 compared to [177Lu]Lu-DOTA.SA.FAPi. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is safe and unveiled new frontiers to treat various end-stage cancer patients with a theranostic approach.

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A Physiologically Based Pharmacokinetic Model for In Vivo Alpha Particle Generators Targeting Neuroendocrine Tumors in Mice

Pharmaceutics ◽

10.3390/pharmaceutics13122132 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2132

Author(s):

Nouran R. R. Zaid ◽

Peter Kletting ◽

Gordon Winter ◽

Vikas Prasad ◽

Ambros J. Beer ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Alpha Particle ◽

Pbpk Model ◽

Absorbed Dose ◽

Whole Body ◽

Physiologically Based Pharmacokinetic ◽

Decay Products ◽

Absorbed Doses ◽

Physiologically Based

In vivo alpha particle generators have great potential for the treatment of neuroendocrine tumors in alpha-emitter-based peptide receptor radionuclide therapy (α-PRRT). Quantitative pharmacokinetic analyses of the in vivo alpha particle generator and its radioactive decay products are required to address concerns about the efficacy and safety of α-PRRT. A murine whole-body physiologically based pharmacokinetic (PBPK) model was developed for 212Pb-labeled somatostatin analogs (212Pb-SSTA). The model describes pharmacokinetics of 212Pb-SSTA and its decay products, including specific and non-specific glomerular and tubular uptake. Absorbed dose coefficients (ADC) were calculated for bound and unbound radiolabeled SSTA and its decay products. Kidneys received the highest ADC (134 Gy/MBq) among non-target tissues. The alpha-emitting 212Po contributes more than 50% to absorbed doses in most tissues. Using this model, it is demonstrated that α-PRRT based on 212Pb-SSTA results in lower absorbed doses in non-target tissue than α-PRRT based on 212Bi-SSTA for a given kidneys absorbed dose. In both approaches, the energies released in the glomeruli and proximal tubules account for 54% and 46%, respectively, of the total energy absorbed in kidneys. The 212Pb-SSTA-PBPK model accelerates the translation from bench to bedside by enabling better experimental design and by improving the understanding of the underlying mechanisms.

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Is nuclear medicine really safe?

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132002000500016 ◽

2002 ◽

Vol 45 (spe) ◽

pp. 115-118

Author(s):

Nicole Colas-Linhart

Keyword(s):

Nuclear Medicine ◽

Human Serum Albumin ◽

Radiation Dose ◽

Serum Albumin ◽

Human Serum ◽

Absorbed Dose ◽

Cellular Level ◽

Whole Body ◽

Absorbed Doses ◽

Standard Models

In nuclear medicine, radiation absorbed dose estimates calculated by standard models at the whole body or organ are very low. At cellular level, however, the heterogeneity of radionuclide distributions of radiation dose patterns may be significant. We present here absorbed doses at cellular level and evaluate their possible impact on the usually assumed risk/benefit relationships in nuclear medicine studies. The absorbed dose values calculated are surprisingly high, and are difficult to interpret. In the present study, we show calculated doses at the cellular level and discuss possible biological consequences, for two radiopharmaceuticals labelled with technetium-99m: human serum albumin microspheres used for pulmonary scintigrapies and HMPAO used to labelled leukocytes.

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Is it necessary to reduce the radioiodine dose in patients with thyroid cancer and renal failure?

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000400011 ◽

2010 ◽

Vol 54 (4) ◽

pp. 413-418 ◽

Cited By ~ 4

Author(s):

José Willegaignon ◽

Verena Pinto Brito Ribeiro ◽

Marcelo Sapienza ◽

Carla Ono ◽

Tomoco Watanabe ◽

...

Keyword(s):

Thyroid Cancer ◽

Dose Adjustment ◽

Absorbed Dose ◽

Whole Body ◽

Half Time ◽

Dialysis Therapy ◽

Absorbed Doses ◽

131I Activity ◽

Dosimetric Data ◽

Higher Doses

The objective of this study were to obtain dosimetric data from a patient with thyroid cancer simultaneously undergoing peritoneal dialysis therapy, so as to determine the appropriate amount of 131I activity to be applied therapeutically. Percentages of radioiodine in the blood and the whole-body were evaluated, and radiation absorbed doses were calculated according to OLINDA/EXM software. Whole-body 131I effective half-time was 45.5 hours, being four times longer than for patients without any renal dysfunction. Bone-marrow absorbed dose was 0.074 mGy/MBq, with ablative procedure maintenance at 3.7 GBq, as the reported absorbed dose was insufficiently restrictive to change the usual amount of radioiodine activity administered for ablation. It was concluded that radioiodine therapeutic-dose adjustment, based on individual patient dosimetry, is an important way of controlling therapy. It also permits the safe and potential delivery of higher doses of radiation to tumors and undesirable tissues, with a minimum of malignant effects on healthy tissues.

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Simplification of Dosimetry in 90Y-Radioembolization Therapy Using Dual Planar Images.

10.21203/rs.3.rs-150596/v1 ◽

2021 ◽

Author(s):

mohammad abuqbeitah ◽

Özgür Akdağ ◽

mustafa demir ◽

sertaç asa ◽

kerim sönmezoğlu

Keyword(s):

Scatter Correction ◽

Absorbed Dose ◽

Whole Body ◽

Whole Body Scan ◽

Body Scan ◽

Absorbed Doses ◽

Significant Difference ◽

Lung Shunt ◽

The Impact ◽

Healthy Liver

Abstract Aim: The purpose was to provide practical and effective method for performing 90Y dosimetry with 99mTc-MAA. The impact of scatter and attenuation correction (AC) on the injected 90Y activity and absorbed doses to critical organs was also further target beyond this study.Material and Methods: 18 patients (F: 3, M: 15) were subjected to 90Y therapy. 99mTc-MAA (111-222 MBq) was injected into the targeted liver, followed by a whole-body scan (WBS) with peak-window at 140 keV (15% width), and one down-scatter window. SPECT/CT scan was acquired over the lungs and liver regions. The lung shunt fractions were fashioned from the standard WBS, scatter corrected WBS, only scatter corrected SPECT and SPECT/CT with attenuation and scatter correction. The absorbed doses to tumor and surrounding healthy tissue were estimated with alternative approaches involving AC-SC (SPECT/CT), NoAC-SC (SPECT), NoAC-NoSC+LSF (SC-WBS), AC-SC+LSF (WBS), and NoAC-NoSC+LSF (WBS).Results: The average LSF deviations between the standard LSF and those obtained from AC-SC, NoAC-SC, and SC-WBS was -50% (-29/-71), -32%(-8/-67), and -45%(-13/80), respectively. The prescribed 90Y activity (GBq/Gy) was decreased by a range of 2-11%, 1-9%, and 2-7% with using LSFs from AC-SC, NoAC-SC, SC-WBS images. The absorbed dose to tumour and healthy liver tissue were calculated as 112±90 Gy and 30±18 Gy/GBq by AC-SC (SPECT/CT), 117±108 and 30±22 by NoAC-SC (SPECT), 110±100 and 31±21 Gy/GBq by NoAC-NoSC+LSF (SC-WBS), 106±84 and 28±17 Gy/GBq by AC-SC+LSF (WBS), while the absorbed dose was 90±85 and 28±20 Gy/GBq by using NoAC-NoSC+ LSF (WBS). Overall, no significant difference (p< 0.05) in the tomour and the health liver dose between all the approaches with/and without scatter correction. However, the scatter correction caused a significant difference in the lung shunt fractions (p <0.05).Conclusion: Scatter correction has a significant effect on the lung shunt fractions, planned activity and number of 90Y treatments. However, a minimal or negligible change was occurred on the absorbed dose to tumours and surrounding healthy liver. The good agreement between SPECT/CT approach, and scatter corrected whole-body scan might be practical and effective route for 90Y dosimetry.

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Evaluation of Radiation dosimetry of 99mTc-HYNIC-PSMA and imaging in prostate cancer

Scientific Reports ◽

10.1038/s41598-020-61129-5 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jianping Zhang ◽

Jiangang Zhang ◽

Xiaoping Xu ◽

Linjun Lu ◽

Silong Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Dosimetry ◽

Tumor Imaging ◽

Absorbed Dose ◽

Ct Images ◽

Tracer Uptake ◽

Whole Body ◽

Imaging Method ◽

Absorbed Doses ◽

Total Body

Abstract This study aims to evaluate the radiation dosimetry of a new technetium-99m‒labelled small-molecule inhibitor of prostate-specific membrane antigen (HYNIC-Glu-Urea-A, 99mTc-HYNIC-PSMA) and its feasibility as a tumor-imaging agent in prostate cancer (PCa) patients. A total of 15 PCa patients were enrolled in this study. For the dosimetry study, 5 PCa patients received whole-body planar scans at 0.5 h, 1 h, 2 h, 4 h and 8 h after 99mTc-HYNIC-PSMA injection. The Dosimetry Toolkit (GE, Milwaukee) was used to process the data and segment the organs in the SPECT/CT images, which were then projected onto planar images. The organ-specific absorbed doses, total-body absorbed doses and 99mTc-HYNIC-PSMA effective doses of patients were calculated using OLINDA/EXM 1.1 software. Whole-body SPECT/CT images were also acquired from additional 10 prostate patients to investigate the feasibility of 99mTc-HYNIC-PSMA for imaging tumors by calculating the ratio of tumor-to-background tracer uptake at 2 h after 740 MBq administration. The total-body absorbed dose was 1.54E-03 ± 2.43E-04 mGy/MBq, and the effective dose was 3.72E-03 ± 4.5E-04 mSv/MBq. Compared to published studies of other similar PSMA tracers and 99mTc-targeted conventional tracers, the absorbed doses of 99mTc-HYNIC-PSMA in all organs showed that it could be used safely in the human body. In addition, 99mTc-HYNIC-PSMA showed high tracer uptake (with a tumor-to-background ratio of 9.42 ± 2.62) in the malignant lesions of PCa patients, making it a promising radiopharmaceutical imaging method for site-specific management of PCa.

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RADT-24. HIGH ABSORBED DOSES OF RHENIUM-186 NANOLIPOSOMES (RNL) IN RECURRENT GBM: A PHASE 1 STUDY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.777 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii186-ii186

Author(s):

Andrew Brenner ◽

John Floyd ◽

Ande Bao ◽

William Phillips ◽

Vibhudutta Awasthi ◽

...

Keyword(s):

Phase 1 ◽

High Specific Activity ◽

Absorbed Dose ◽

External Beam Radiation ◽

Whole Body ◽

Recurrent Glioma ◽

Normal Brain ◽

Beam Radiation ◽

Absorbed Doses ◽

The Mean

Abstract INTRODUCTION While external beam radiation therapy (EBRT) remains a central component of the management of primary brain tumors, it is limited by tolerance of the surrounding normal brain tissue. Nanoliposomal BMEDA-chelated-186Rhenium (RNL™) permits the delivery of beta-emitting radiation of high specific activity with excellent retention in the tumor. We report on the phase 1 results in recurrent glioma. METHODS A phase 1 dose-escalation study of RNL in recurrent glioma utilizing a standard 3 + 3 design was undertaken to determine the maximum tolerated dose of RNL following stereotactic biopsy. RNL is administered with the BrainLab Flexible Catheter by convection enhanced delivery (CED) with placement guided using iPlan Flow and the Varioguide system. Infusion is followed under whole body planar imaging and SPECT/CT. Repeat SPECT/CT imaging is performed immediately following, and at 1, 3, 5, and 8 days after RNL infustion to obtain dosimetry and distribution. RESULTS Thirteen patients have been treated to-date, 12 were recurrent glioblastoma, and 54% failed treatment with bevacizumab. The infused dose was progressively increased from 1.0 mCi to 13.4 mCi and the volume of infusate from 1.0 mL to 5.28 mL using 1 – 2 CED catheters. The mean absorbed dose to the distribution volume was 175 Gy (CI 97 – 254). The maximum absorbed dose to the tumor volume was 593 Gy. The mean retention of the administered dose at 24 hours was 61.4% (CI 45.4 – 77.5). The therapy has been well tolerated and no dose-limiting toxicity has been observed with no treatment related adverse effects despite markedly higher absorbed doses than EBRT in patients with prior treatment. The plan is to increase the dose to 22.3 mCi and the infusate volume to 8.8 mL. CONCLUSION Intratumoral RNL can deliver up to twenty times the absorbed dose of radiation administered by EBRT without significant toxicity.

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Observation of morphological abnormalities in silkworm pupae after feeding 137CsCl-supplemented diet to evaluate the effects of low dose-rate exposure

Scientific Reports ◽

10.1038/s41598-020-72882-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Sota Tanaka ◽

Tadatoshi Kinouchi ◽

Tsuguru Fujii ◽

Tetsuji Imanaka ◽

Tomoyuki Takahashi ◽

...

Keyword(s):

Dose Rate ◽

Low Dose ◽

Absorbed Dose ◽

Dose Effect ◽

Whole Body ◽

High Concentration ◽

Morphological Abnormalities ◽

Low Dose Rate ◽

Absorbed Doses ◽

Silkworm Pupae

Abstract Since the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, morphological abnormalities in lepidopteran insects, such as shrinkage and/or aberration of wings, have been reported. Butterflies experimentally exposed to radiocesium also show such abnormalities. However, because of a lack of data on absorbed dose and dose–effect relationship, it is unclear whether these abnormalities are caused directly by radiation. We conducted a low dose-rate exposure experiment in silkworms reared from egg to fully developed larvae on a 137CsCl-supplemented artificial diet and estimated the absorbed dose to evaluate morphological abnormalities in pupal wings. We used 137CsCl at 1.3 × 103 Bq/g fresh weight to simulate 137Cs contamination around the FDNPP. Absorbed doses were estimated using a glass rod dosimeter and Monte Carlo particle transport simulation code PHITS. Average external absorbed doses were approximately 0.24 (on diet) and 0.016 mGy/day (near diet); the average internal absorbed dose was approximately 0.82 mGy/day. Pupal wing structure is sensitive to radiation exposure. However, no significant differences were observed in the wing-to-whole body ratio of pupae between the 137CsCl-exposure and control groups. These results suggest that silkworms are insensitive to low dose-rate exposure due to chronic ingestion of high 137Cs at a high concentration.

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Patient-Specific Three Dimensional (3D) Dosimetry for 90Y Ibritumomab Tiutexan (Zevalin®) in Patients with Follicular Lymphoma.

Blood ◽

10.1182/blood.v106.11.4780.4780 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4780-4780

Author(s):

Karine Assié ◽

Arnaud Dieudonné ◽

Isabelle Gardin ◽

Irène Buvat ◽

Hervé Tilly ◽

...

Keyword(s):

Follicular Lymphoma ◽

Ct Scan ◽

Left Kidney ◽

Whole Body ◽

Patient Specific ◽

Quantitative Spect ◽

3D Dosimetry ◽

Absorbed Doses ◽

Specific Protocol ◽

True Activity

Abstract Objectives: Dosimetry calculations for radioimmunotherapy are usually performed using a two dimensional (2D) protocol based on planar whole body (WB) scintigraphy and fixed organ masses derived from the MIRD anthropomorphic model (Wiseman GA et al., J Nucl Med2003:44;465–74). We compared the absorbed dose obtained with this method with an approach involving patient-specific 3D dosimetry based on quantitative SPECT and patient organs mass estimation. Methods: Five patients with follicular lymphoma in partial or complete remission underwent a CT scan, and five successive WB and SPECT scans at day 0 (D0) 1 hour, D0 4 hours, D1, D4 and D6 after injection of 111In ibritumomab tiutexan (185 MBq). WB scans were used to estimate the activity in the liver, spleen and kidneys. SPECT images were reconstructed using a quantitative processing including corrections for scatter, attenuation, and partial volume effect. The organs mass and activity values were estimated in 3D volumes of interest manually drawn on the CT scan and registered to the SPECT scan. Absorbed doses after administration of 15 MBq/kg of 90Y ibritumomab tiutexan were derived from both 111In WB and SPECT data accounting for the fractions of injected activity measured in each organ at the five time points. Results: The mean differences between the organs mass estimated from the patient CT and the MIRD anthropomorphic model were 8%, 105% and 12% for liver, spleen and kidneys respectively. Measurements on an abdominal phantom filled with 111In showed that errors in organ activity estimates ((estimated activity - true activity)/true activity) for WB and SPECT protocols, were 37% and −6% respectively in the liver, 20% and −10% in the spleen, −26% and −23% in the left kidney, and 47% and −9% in the right kidney. Patient liver, spleen and kidney activity values determined from the SPECT scans were on average 35%, 60% and 39% less than those found from the WB scans. The absorbed doses calculated with the 3D patient-specific protocol were less than those calculated with the 2D protocol, by 46±14%, 77±14% and 70±22% in the liver, spleen and kidneys respectively, except in one patient kidney where SPECT dose exceeded WB dose by 2%. Conclusions: Accounting for patient-specific organ mass and using SPECT activity quantification have a great impact on estimated absorbed doses of 90Y ibritumomab tiutexan if compared with the 2D protocol. This method could improve the correlation between dosimetry and clinical consequences of this treatment, especially in view of dose escalation with stem cell rescue.

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First-In-Human Results On The Biodistribution, Pharmacokinetics, And Dosimetry of [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2 in Patients with Various End-stage Cancers

10.21203/rs.3.rs-786088/v1 ◽

2021 ◽

Author(s):

Sanjana Ballal ◽

Madhav Prasad Yadav ◽

Euy Sung Moon ◽

Vasko S Kramer ◽

Frank Roesch ◽

...

Keyword(s):

Urinary Bladder ◽

Gall Bladder ◽

Oral Mucosa ◽

Absorbed Dose ◽

Left Colon ◽

Whole Body ◽

Lacrimal Glands ◽

Right Colon ◽

Absorbed Doses ◽

End Stage

Abstract Purpose: The present study aimed to evaluate and compare the biodistribution, pharmacokinetics, dosimetry of [177Lu]Lu-DOTA.SA.FAPi, and [177Lu]Lu-DOTAGA.(SA.FAPi)2 in patients with various cancers.Methods: The FAPi agents, [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2 were administered in two different groups of patients. Three patients (mean age; 50 years) were treated with a median cumulative activity of 2.96 GBq (IQR: 2.2 – 3 GBq) [177Lu]Lu-DOTA.SA.FAPi and seven (mean age; 51 years) were treated with 1.48 GBq (IQR: 0.6 – 1.5) of [177Lu]Lu-DOTAGA.(SA.FAPi)2. Patients in both the groups underwent serial imaging whole-body planar and SPECT/CT scans that were acquired between 1 hour and 168 hours post-injection (p.i.)The residence time and absorbed dose estimate in the source organs and tumor were calculated using OLINDA/EXM 2.2 software. Time versus activity graphs were plotted to determine the effective half-life (Te) in the whole body and lesions for both the radiotracers. Results: Physiological uptake of [177Lu]Lu-DOTA.SA.FAPi was observed in the kidneys, colon, pancreas, liver, gall bladder, oral mucosa, lacrimal glands, and urinary bladder contents. Physiological biodistribution of [177Lu]Lu-DOTAGA.(SA.FAPi)2 involved liver, gall bladder, colon, pancreas, kidneys, and urinary bladder contents, lacrimal glands, oral mucosa, and salivary glands. The whole body effective dose for [177Lu]Lu-DOTAGA.(SA.FAPi)2 was significantly higher than [177Lu]Lu-DOTA.SA.FAPi [2.26E-01 ± 1.24E-01; vs. 6.22E-02 ± 9.96E-03 mSv/MBq, P-0.058). In the [177Lu]Lu-DOTA.SA.FAPi group, the highest absorbed dose were noted in the Kidneys (0.618 ± 0.015 Gy/GBq), followed by a colon (right colon: 0.472 Gy/GBq and left colon: 0.43 Gy/GBq). In the [177Lu]Lu-DOTAGA.(SA.FAPi)2 group, the colon received the highest absorbed dose (right colon: 1.16 Gy/GBq and left colon: 2.87 Gy/GBq), and demonstrated a significantly higher mean absorbed dose than [177Lu]Lu-DOTA.SA.FAPi (P < 0.011). [177Lu]Lu-DOTAGA.(SA.FAPi)2 had significantly longer median whole-body Te compared to that of [177Lu]Lu-DOTA.SA.FAPi [46.2 h (IQR: 38.5 – 70.1) vs. 23.1 h (IQR: 17.8 – 31.5); P-0.0167]. The median absorbed doses to the lesions were 6.03E-01(IQR: 2.30E-01 - 1.81E+00) Gy/GBq and 6.70E+00 (IQR: 3.40E+00 - 4.9E+01) Gy/GBq dose per cycle in the [177Lu]Lu-DOTA.SA.FAPi, and [177Lu]Lu-DOTAGA.(SA.FAPi)2 groups, respectively. Conclusion: The first clinical dosimetry study demonstrated significantly higher tumor absorbed doses with [177Lu]Lu-DOTAGA.(SA.FAPi)2 compared to [177Lu]Lu-DOTA.SA.FAPi. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is safe and unveiled new frontiers to treat various end-stage cancer patients with a theranostic approach.

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