Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent / Produção, controle de qualidade, avaliação de biodistribuição e avaliação da dose preliminar de [177Lu] -tetra complexo fenil porfirina como um possível agente terapêutico

Due to interesting therapeutic properties of ¹⁷⁷Lu and tumor avidity of tetraphenyl porphyrins (TPPs), ¹⁷⁷Lu-tetraphenyl porphyrin was developed as a possible therapeutic compound. ¹⁷⁷Lu of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu₂O₃sample with thermal neutron flux of 4 × 10¹³ n.cm^-2.s^-1. Tetraphenyl porphyrin was synthetized and labeled with ¹⁷⁷Lu. Radiochemical purity of the complex was studied using Instant thin layer chromatography (ITLC) method. Stability of the complex was checked in final formulation and human serum for 48 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied up to 7 d. The absorbed dose of each human organ was calculated by medical internal radiation dose (MIRD) method. A detailed comparative pharmacokinetic study was performed for ¹⁷⁷Lu cation and [¹⁷⁷Lu]-TPP. The complex was prepared with a radiochemical purity: >97±1% and specific activity: 970-1000 MBq/mmol. Biodistribution data and dosimetric results showed that all tissues receive approximately an insignificant absorbed dose due to rapid excretion of the complex through the urinary tract. [¹⁷⁷Lu]-TPP can be an interesting tumor targeting agent due to low liver uptake and very low absorbed dose of approximately 0.036 to the total body of human...

Devido às propriedades interessantes do ¹⁷⁷Lu e da avidez tumoral das tetrafenil porfirinas (TPP), desenvolveu-se a ¹⁷⁷Lu-tetrafenil porfirina como composto terapêutico potencial. ¹⁷⁷Lu de atividade específica de 2,6-3 GBq/mg foi obtido por irradiação de amostra de Lu₂O₃ com fluxo térmico de nêutrons de 4 × 10¹³ n.cm^-2.s^-1. Sintetizou-se a tetrafenil porfirina e marcou-se com ¹⁷⁷Lu. A pureza radioquímica do complexo foi estudada usando método de Cromatografia Instantânea de Camada Delgada ( ITLC). A estabilidade do complexo foi checada na formulação final e no ser humano por 48 h. A biodistribuição do composto marcado em órgãos vitais de ratos do tipo selvagem foi estudada por mais de 7 dias. A dose absorvida para cada órgão humano foi calculada pelo método da Dose Médica de Radiação Interna (MIRD). Estudo farmacocinético comparativo detalhado foi efetuado para o cátion ¹⁷⁷Lu e para o [¹⁷⁷Lu]-TPP. O complexo foi preparado com pureza radioquímica >97±1% e atividade específica de 970-1000 MBq/mmol. Os dados de biodistribuição e os resultados dosimétricos mostraram que todos os tecidos receberam uma dose absorvida aproximadamente insignificante devido à rápida excreção do complexo pelo trato urinário. O [¹⁷⁷Lu]-TPP pode ser um agente interessante de direcionamento do tumor devido à baixa captação pelo fígado e pela dose bem baixa absorvida, de, aproximadamente, 0,036 do corpo humano total...

Dosimetry and MIRD for Re-188 Liquid Balloons / 대한핵의학회잡지

Re-188 is suitable for endovascular liquid-balloon brachytherapy for the prevention of restenosis after angioplasty. Re-188 was concentrated to 3700 MBq/ml and labeled with DTPA. According to dosimetric calculation, it took 420 seconds using Re-188 solution with concentration of 3700 MBq/ml to irradiate 17.6 Gy to the target at 1 mm from the balloon surface. Software was made to estimate the irradiation time. MIRD calculation with dynamic bladder model yielded the whole body dose of Re-188-DTPA as 0.005mGy/MBq in case of balloon rupture and release of the whole amount into the blood.

Radiation Absorbed Dose Measurement after I-131 Metaiodobenzylguanidine Treatment in a patient with Pheochromycytoma / 대한핵의학회잡지

PURPOSE: The measurement of radiation absorbed dose is useful to predict the response after I-131 labeled metaiodobenzylguanidine (MIBG) therapy and determine therapy dose in patients with unresectable or malignant pheochromocytoma. We estimated the absorbed dose in tumor tissue after high dose I-131 MIBG in a patient with pheochromocytoma using a gamma camera and Medical Internal Radiation Dose (MIRD) formula. MATERIALS AND METHODS: A 64-year old female patient with pheochromocytoma who had multiple metastases of mediastinum, right kidney and periaortic lymph nodes, received 74 GBq (200 mCi) of I-131 MIBG. We obtained anterior and posterior images at 0.5, 16, 24, 64 and 145 hours after treatment. Two standard sources of 37 and 74 MBq of I-131 were imaged simultaneously. Cummulated I-131 MIBG uptake in tumor tissue was calculated after the correction of background activity, attenuation, system sensitivity and count loss at a high count rate. RESULTS: The calculated absorbed radiation dose was 32-63 Gy/ 74 GBq, which was lower than the known dose for tumor remission (150-200 Gy). Follow-up studies at 1 month showed minimally reduced tumor size on computed tomography, and mildly reduced I-131 MIBG uptake. CONCLUSION: We estimated radiation absorbed dose after therapeutic I-131 MIBG using a gamma camera and MIRD formula, which can be peformed in a clinical nuclear medicine laboratory. Our RESULTS suggest that the measurement of radiation absorbed dose in I-131 MIBG therapy is feasible as a routine clinical practice that can guide further treatment plan. The accuracy of dose measurement and correlation with clinical outcome should be evaluated further.

Dosimetry and Medical Internal Radiation Dose of Re-188-DTPA for Endovascular Balloon Brachytherapy Against Restenosis after Coronary Angioplasty / 대한핵의학회잡지

PURPOSE: Liquid beta emitter filled in angioplasty balloon could be used to perform endovascular balloon brachytherapy to prevent coronary artery restenosis. We investigated the dosimetry for Re-188-DTPA liquid-filled balloon and medical internal radiation dosimetry in case of balloon leakage. MATERIALS AND METHODS: We estimated radiation dose from an angioplasty balloon (20 mm lengfh, 3 mm diameter cylinder) to the adjacent vessel wall using Monte Carlo EGS4 code. We obtained time-activity curves of kidneys in normal dog and calculated Tmax, T1/2. Using MIRDOSE3 program, we estimated absorbed doses to the major organs (kidneys, bladder) and the whole body when we assumed that balloon leaked all the isotope contained. RESULTS: The radiation dose was 17.5 Gy at the balloon surface when we applied 3,700 MBq/ml of Re-188 for 100 seconds. Fifty percent of the energy deposited within 1 mm from the balloon surface. The estimated internal dose to the whole body was 0.005 mGy/MBq and 18.5 mGy for the spillage of 3,700 MBq of Re-188. CONCLUSION: We suggest that Re-188-DTPA can be used for endovascular balloon brachytherapy to inhibit coronary artery restenosis after angioplasty with tolerable whole body radiation dose in case of balloon rupture.